九州大学 研究者情報
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増田 智先(ますだ さとひろ) データ更新日:2018.06.28

教授 /  九州大学病院 薬剤部 薬剤部・医病


主な研究テーマ
薬物による毒性発現の分子機構解明とそれに基づく対策法の確立
キーワード:薬物有害反応、薬物トランスポーター、代謝酵素、受容体、リン酸化
2010.04.
免疫抑制薬の個別化投与設計法の構築
キーワード:肝移植、腎移植、潰瘍性大腸炎、クローン病、カルシニューリン阻害薬、mTOR阻害薬、血中濃度モニタリング、遺伝子多型、
1999.11.
安全性バイオマーカーの探索と臨床応用
キーワード:尿中バイオマーカー、血清バイオマーカー、低分子RNA、メタボロミクス
2007.06.
薬物性腎障害の分子機構解明
キーワード:薬物トランスポーター、急性腎不全
1997.04.
従事しているプロジェクト研究
移植肝障害のバイオマーカー創製(最先端・次世代研究開発支援プログラム)
2012.02~2016.03, 代表者:増田智先, 九州大学病院
http://www.jsps.go.jp/j-jisedai/data/life/LS073_outline.pdf.
研究業績
主要原著論文
1. Yamamoto, S., S. Ushio, N. Egashira, T. Kawashiri, S. Mitsuyasu, H. Higuchi, N. Ozawa, K. Masuguchi, Y. Ono and S. Masuda., Excessive spinal glutamate transmission is involved in oxaliplatin-induced mechanical allodynia: a possibility for riluzole as a prophylactic drug., SCIENTIFIC REPORTS , 10.1038/s41598-017-08891-1 , 7, 9661, 2017.08, Oxaliplatin, a chemotherapy medication, causes severe peripheral neuropathy. Although oxaliplatin-induced peripheral neuropathy is a dose-limiting toxicity, a therapeutic strategy against its effects has not been established. We previously reported the involvement of N-methyl-D-aspartate receptors and their intracellular signalling pathway in oxaliplatin-induced mechanical allodynia in rats. The aim of this study was to clarify the involvement of spinal glutamate transmission in oxaliplatin-induced mechanical allodynia. In vivo spinal microdialysis revealed that the baseline glutamate concentration was elevated in oxaliplatin-treated rats, and that mechanical stimulation of the hind paw markedly increased extracellular glutamate concentration in the same rats. In these rats, the expression of glutamate transporter 1 (GLT-1), which plays a major role in glutamate uptake, was decreased in the spinal cord. Moreover, we explored the potential of pharmacological therapy targeting maintenance of extracellular glutamate homeostasis. The administration of riluzole, an approved drug for amyotrophic lateral sclerosis, suppressed the increase of glutamate concentration, the decrease of GLT-1 expression and the development of mechanical allodynia. These results suggest that oxaliplatin disrupts the extracellular glutamate homeostasis in the spinal cord, which may result in neuropathic symptoms, and support the use of riluzole for prophylaxis of oxaliplatin-induced mechanical allodynia..
2. Yamada, T., T. Kubota, M. Yonezawa, H. Nishio, S. Kanno, T. Yano, D. Kobayashi, N. Egashira, H. Takada, T. Hara and S. Masuda., Evaluation of Teicoplanin Trough Values After the Recommended Loading Dose in Children With Associated Safety Analysis., PEDIATRIC INFECTIOUS DISEASE JOURNAL , 10.1097/INF.0000000000001456, 36, 4, 398-400, 2017.04, Background: This study evaluated whether the recommended teicoplanin loading dose (3 loading doses of 10 mg/kg every 12 hours) achieves a 15-30 mu g/mL trough levels in 26 children (2-16 years). In addition, we examined the incidences of renal impairment and hepatic dysfunction in children treated with teicoplanin.

Methods: This retrospective study was conducted between October 2008 and March 2014.

Results: The percentage of patients with a trough level <10 and <15 mu g/mL were 15.4% (4/26) and 46.2% (12/26), respectively. There were significant correlations between age and concentration/cumulative loading dose (C/D) ratio (P = 0.045), serum creatinine and C/D ratio (P < 0.001) and estimated glomerular filtration rate and C/D ratio (P = 0.005). Serum creatinine was significantly lower when trough levels were < 15 mu g/mL compared with >= 15 mu g/mL. The incidences of renal impairment and hepatic dysfunction were 2.3% and 5.8%, respectively, with no significant difference between < 20 and >= 20 mu g/mL trough-level groups.

Conclusions: The recommended loading dose may be insufficient to achieve 15-30 mu g/mL in children with normal renal function. In addition, the target trough level >= 20 mu g/mL for deep-seated infections seems to be safe in children..
3. Suetsugu, K., H. Ikesue, T. Miyamoto, M. Shiratsuchi, N. Yamamoto-Taguchi, Y. Tsuchiya, K. Matsukawa, M. Uchida, H. Watanabe, K. Akashi and S. Masuda., Analysis of the variable factors influencing tacrolimus blood concentration during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation., INTERNATIONAL JOURNAL OF HEMATOLOGY , 10.1007/s12185-016-2135-7, 105, 3, 361-368, 2017.03, The aim of this retrospective study was to identify variable factors affecting tacrolimus blood concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n = 73). The blood concentration/dose ratio of tacrolimus immediately before the change from continuous infusion (C/Div) was compared with that between 3 and 5 days after the change to oral administration (C/Dpo). Median (C/Dpo)/(C/Div) was 0.21 (range 0.04-0.58). Multiple regression analysis showed that concomitant use of oral itraconazole or voriconazole significantly increased the (C/Dpo)/(C/Div) of tacrolimus (p = 0.002), probably owing to the inhibition of enterohepatic cytochrome P450 3A4. In addition, 5 of 18 (28%) patients who had the lowest quartile (C/Dpo)/(C/Div) values developed acute graft-versus-host-disease (GVHD), which was significantly higher than in others [5 of 55 (9%) patients, p = 0.045]. Although the switch from intravenous to oral administration at a ratio of 1:5 appeared to be appropriate, a lower conversion ratio was suitable in patients taking oral itraconazole or voriconazole. In patients whose blood concentration decreases after the switch, the development of GVHD should be monitored and tacrolimus dosage should be readjusted to maintain an appropriate blood concentration..
4. Sakamoto, Y ; Yano, T ; Hanada, Y; Takeshita, A; Inagaki, F; Masuda, S; Matsunaga, N ; Koyanagi, S ; Ohdo, S ., Vancomycin induces reactive oxygen species-dependent apoptosis via mitochondrial cardiolipin peroxidation in renal tubular epithelial cells, EUROPEAN JOURNAL OF PHARMACOLOGY, 10.1016/j.ejphar.2017.02.025, 800, 48-56, 2017.05, Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death. In the present study, VCM caused production of mitochondrial reactive oxygen species and peroxidation of the mitochondrial phospholipid cardiolipin that was reversed by administration of the mitochondrial uncoupler carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP). FCCP also significantly suppressed VCM-induced depolarization of the mitochondrial membrane and apoptosis. Moreover, the lipophilic antioxidant vitamin E and a mitochondria-targeted antioxidant, mitoTEMPO, also significantly suppressed VCM-induced depolarization of mitochondrial membrane and apoptosis, whereas vitamin C, n-acetyl cysteine, or glutathione did not provide significant protection. These findings suggest that peroxidation of the mitochondrial membrane cardiolipin mediated the VCM-induced production of intracellular reactive oxygen species and initiation of apoptosis in LLC-PK1 cells. Furthermore, regulation of mitochondrial function using a mitochondria-targeted antioxidant, such as mitoTEMPO, may constitute a potential strategy for mitigation of VCM-induced proximal tubular epithelial cell injury..
5. Murata, K., Y. Motomura, T. Tanaka, S. Kanno, T. Yano, M. Onimaru, A. Shimoyama, H. Nishio, Y. Sakai, M. Oh-Hora, H. Hara, K. Fukase, H. Takada, S. Masuda, S. Ohga, S. Yamasaki and T. Hara., Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signaling pathway in a murine model of Kawasaki disease., Clin Exp Immunol, 10.1111/cei.13002 , 190, 1, 54-67, 2017.10, Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9(-/-) mice but not in MyD88(-/-) mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD..
6. Yoshimatsu, Hiroki, Yonezawa, Atsushi, Yamanishi, Kaori, Yao, Yoshiaki, Sugano, Kumiko, Nakagawa, Shunsaku, Imai, Satoshi, Omura, Tomohiro, Nakagawa, Takayuki, Yano, Ikuko, Satohiro Masuda, Inui, Ken-ichi, Matsubara, Kazuo, Disruption of Slc52a3 gene causes neonatal lethality with riboflavin deficiency in mice, Scientific reports, 10.1038/srep27557, 6, 2016.06, Homeostasis of riboflavin should be maintained by transporters. Previous in vitro studies have elucidated basic information about riboflavin transporter RFVT3 encoded by SLC52A3 gene. However, the contribution of RFVT3 to the maintenance of riboflavin homeostasis and the significance in vivo remain unclear. Here, we investigated the physiological role of RFVT3 using Slc52a3 knockout (Slc52a3-/-) mice. Most Slc52a3-/- mice died with hyperlipidemia and hypoglycemia within 48 hr after birth. The plasma and tissue riboflavin concentrations in Slc52a3-/- mice at postnatal day 0 were dramatically lower than those in wild-type (WT) littermates. Slc52a3-/- fetuses showed a lower capacity of placental riboflavin transport compared with WT fetuses. Riboflavin supplement during pregnancy and after birth reduced neonatal death and metabolic disorders. To our knowledge, this is the first report to indicate that Rfvt3 contributes to placental riboflavin transport, and that disruption of Slc52a3 gene caused neonatal mortality with hyperlipidemia and hypoglycemia owing to riboflavin deficiency..
7. Yamada, Takaaki, Ueda, Mitsuyo, Egashira, Nobuaki, Zukeyama, Nina, Kuwahara, Jun, Satohiro Masuda, Involvement of intracellular cAMP in epirubicin-induced vascular endothelial cell injury, Journal of pharmacological sciences, 10.1016/j.jphs.2015.12.010, 130, 1, 33-37, 2016.01, We investigated the involvement of intracellular cAMP in endothelial cell injury induced by epirubicin. Epirubicin-induced decrease in cell viability and increase in caspase-3/7 activity were reversed by a cAMP analog dibutyryl cAMP (DBcAMP) or an activator of adenylate cyclase forskolin concomitant with a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, epirubicin-induced elevation of lipid peroxide levels was attenuated by DBcAMP. Interestingly, the exposure of epirubicin decreased intracellular cAMP levels before the onset of epirubicin-induced production of lipid peroxidation. These results suggest that intracellular cAMP plays an important role in epirubicin-induced endothelial cell injury..
8. Yahata, Hideaki, Kobayashi, Hiroaki, Sonoda, Kenzo, Shimokawa, Mototsugu, Ohgami, Tatsuhiro, Saito, Toshiaki, Ogawa, Shinji, Sakai, Kunihiro, Ichinoe, Akimasa, Ueoka, Yousuke, Hasuo, Yasuyuki, Nishida, Makoto, Satohiro Masuda, Kato, Kiyoko, Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin, INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 10.1007/s10147-015-0928-y, 21, 3, 491-497, 2016.06, BACKGROUND: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. METHODS: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively. RESULTS: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group. CONCLUSION: The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy..
9. Tanaka, Satona, Chen-Yoshikawa, Toyofumi F, Kajiwara, Moto, Menju, Toshi, Ohata, Keiji, Takahashi, Mamoru, Kondo, Takeshi, Hijiya, Kyoko, Motoyama, Hideki, Aoyama, Akihiro, Satohiro Masuda, Date, Hiroshi, Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung, ANNALS OF THORACIC SURGERY, 10.1016/j.athoracsur.2016.05.037, 102, 5, 1717-1724, 2016.11, PURPOSE: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. METHODS: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. RESULTS: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. CONCLUSIONS: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females..
10. Shipkova, Maria, Hesselink, Dennis A, Holt, David W, Billaud, Eliane M, van Gelder, Teun, Kunicki, Pawel K, Brunet, Merce, Budde, Klemens, Barten, Markus J, De Simone, Paolo, Wieland, Eberhard, Millan Lopez, Olga, Satohiro Masuda, Seger, Christoph, Picard, Nicolas, Oellerich, Michael, Langman, Loralie J, Morris, Raymond G, Thompson, Carol, Therapeutic Drug Monitoring of Everolimus: A Consensus Report, THERAPEUTIC DRUG MONITORING, 38, 2, 143-169, 2016.04, PURPOSE: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. METHODS: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. RESULTS: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. CONCLUSIONS: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females..
11. Onoue, Haruka, Yano, Ikuko, Tanaka, Atsuko, Itohara, Kotaro, Hanai, Akiko, Ishiguro, Hiroshi, Motohashi, Hideyuki, Satohiro Masuda, Matsubara, Kazuo, Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach, EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 10.1007/s00228-016-2031-3, 72, 6, 703-710, 2016.06, PURPOSE: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. METHODS: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. RESULTS: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. CONCLUSIONS: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females..
12. Miura, M, Satohiro Masuda, Egawa, H., Yuzawa, K, Matsubara, K, Inter-laboratory Variability of Current Immunoassay Methods for Tacrolimus Among Japanese Hospitals, Biological & pharmaceutical bulletin, 10.1248/bpb.b16-00249, 39, 8, 1331-1337, 2016.06.
13. Mio Kikuchi, Yuki Okuda, Yoshihide Ueda, Yuki Nishioka, Miwa Uesugi, Emina Hashimoto, Tamotsu Takahashi, Tomoki Kawai, Sachiyo Hashi, Haruka Shinke, Tomohiro Omura, Atsushi Yonezawa, Takashi Ito, Yasuhiro Fujimoto, Toshimi Kaido, Tsutomu Chiba, Shinji Uemoto, Kazuo Matsubara, Satohiro Masuda, Successful Telaprevir Treatment in Combination of Cyclosporine against Recurrence of Hepatitis C in the Japanese Liver Transplant Patients, 37, 3, 417-423, 2014.03, Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150-200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24-0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection..
14. Ayami Tsuchimoto, Haruka SHinke, Miwa Uesugi, Mio Kikuchi, Emina Hashimoto, Tomoko Sato, Yasuhiro Ogura, Koichiro Hata, Yasuhiro Fujimoto, Toshimi Kaido, Junji Kishimoto, Motoko Yanagita, Kazuo Matsubara, Shinji Uemoto, Satohiro Masuda, Urinary neutrophil gelatinase-associated lipocalin: a useful biomarker for tacrolimus-induced acute kidney injury in liver transplant patients, PLoS ONE, 10.1371/journal.pone.0110527, 9, 10, e110527, 2014.10, Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. Urine samples were collected from 31 patients after living-donor liver transplantation (LDLT). Twenty recipients developed tacrolimus-induced AKI. After the initiation of tacrolimus therapy, urine samples were collected on postoperative days 7, 14, and 21. In patients who experienced AKI during postoperative day 21, additional spot urine samples were collected on postoperative days 28, 35, 42, 49, and 58. The 8 healthy volunteers, whose renal and liver functions were normal, were asked to collect their blood and spot urine samples. The urinary levels of NGAL, monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without, while those of interleukin-18, osteopontin, cystatin C and clusterin did not differ between the 2 groups. The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800-0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients..
15. Miwa Uesugi, Mio Kikuchi, Haruka Shinke, Tomohiro Omura, Atsushi Yonezawa, Kazuo Matsubara, Yasuhiro Fujimoto, Shinya Okamoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda, Impact of cytochrome P450 3A5 polymorphism in graft livers on the frequency of acute cellular rejection in living-donor liver transplantation, Pharmacogenetics and Genomics, 10.1097/fpc.0000000000000060, 24, 7, 356-366, 2014.07, OBJECTIVE: We investigated whether the cytochrome P450 3A5*3 (CYP3A5*3) genotype affects tacrolimus pharmacokinetics and the risk of acute cellular rejection in living-donor liver transplant patients in Japan.
MATERIALS AND METHODS:
Between July 2004 and June 2011, we enrolled 410 living-donor liver transplant patients receiving tacrolimus. Biopsy specimens of intestinal mucosa and graft liver at surgery were obtained to examine the mRNA expression of CYP3A subfamilies as well as the genotyping of CYP3A5*3 polymorphism.
RESULTS:
The CYP3A5 genotype in the native intestine had no significant effect on the occurrence of acute cellular rejection between postoperative days 14 and 23 in cases with identical or compatible ABO blood types (11.5% for the CYP3A5*1 allele vs. 7.4% for CYP3A5*3/*3; P=0.2643), although the concentration/dose ratio of tacrolimus was significantly higher in patients with the intestinal CYP3A5*3/*3 genotype than in those with the CYP3A5*1 allele for 5 post-transplant weeks. However, patients who received a graft liver with the CYP3A5*1 allele showed a higher rate of acute cellular rejection than those who received a graft liver with the CYP3A5*3/*3 genotype (14.5 vs. 5.7%; P=0.0134). The relative risk for acute cellular rejection associated with the CYP3A5*1 liver allele was 2.629 (P=0.018, Cox regression model). Consequently, graft liver CYP3A5*1 genotype might increase the risk for acute cellular rejection after living-donor liver transplantation, possibly by associating with the local hepatic tacrolimus concentration.
CONCLUSIONS:
The target level of tacrolimus may be affected by the CYP3A5*3 genotype of the liver, rather than by that of the small intestine, after postoperative day 14..
16. Takaaki Kodawara, Satohiro Masuda, Yoshitaka Yano, Kazuo Matsubara, Toshiaki Nakamura, Mikio Masada, Inhibitory effect of ciprofloxacin on β-glucuronidase-mediated deconjugation of mycophenolic acid glucuronide, Biopharm Drug Dispos, 10.10022/bdd1894, 2014.05, The interaction between mycophenolate (MPA) and quinolone antibiotics such as ciprofloxacin is considered to reduce the enterohepatic recycling of MPA, which is biotransformed in the intestine from MPA glucuronide (MPAG) conjugate excreted via the biliary system; however, the molecular mechanism underlying this biotransformation of MPA is still unclear. In this study, we established an in vitro system to evaluate β-glucuronidase-mediated deconjugation and examined the influence of ciprofloxacin on the enzymatic deconjugation of MPAG and MPA resynthesis. Resynthesis of MPA via deconjugation of MPAG increased in a time-dependent manner from 5 to 60 min in the presence of β-glucuronidase. Ciprofloxacin and phenolphthalein-β-D-glucuronide (PhePG), a typical β-glucuronidase substrate, significantly decreased the production of MPA from MPAG in the β-glucuronidase-mediated deconjugation system. In addition, enoxacin significantly inhibited the production of MPA from MPAG, while levofloxacin and ofloxacin had no inhibitory effect on MPA synthesis. Pharmacokinetic analysis revealed that ciprofloxacin showed a dose-dependent inhibitory effect on MPA production from MPAG via β-glucuronidase with a half-maximal inhibitory concentration (IC50) value of 30.4 µM. While PhePG inhibited the β-glucuronidase-mediated production of MPA from MPAG in a competitive manner, ciprofloxacin inhibited MPA synthesis via noncompetitive inhibition. These findings suggest that reduction in the serum MPA concentration during the co-administration of ciprofloxacin is at least in part due to the decreased enterohepatic circulation of MPA because of noncompetitive inhibition of deconjugation of MPAG by intestinal β-glucuronidase..
17. Sachiyo Hashi, Satohiro Masuda, Mio Kikuchi, Miwa Uesugi, Ikuko Yano, Tomohiro Omura, Atsushi Yonezawa, Yasuhiro Fujimoto, Kohei Ogawa, Toshimi Kaido, Shinji Uemoto, Kazuo Matsubara, Assessment of Four Methodologies (Microparticle Enzyme Immunoassay, Chemiluminescent Enzyme Immunoassay, Affinity Column-Mediated Immunoassay, and Flow Injection Assay-Tandem Mass Spectrometry) for Measuring Tacrolimus Blood Concentration in Japanese Liver Transplant Recipients, TRANSPLANTATION PROCEEDINGS, 10.1016/j.transproceed.2013.11.060, 46, 3, 758-760, 2014.04, Therapeutic drug monitoring (TDM) and subsequent dosage adjustment for individual patients in the treatment with tacrolimus are required after liver transplantation to prevent rejection and over-immunosuppression, which leads to severe infection and adverse reactions including nephrotoxicity. The purpose of this study was to evaluate the analytical performance among commercially available immunoassay methods, which were microparticle enzyme immunoassay (MEIA), chemiluminescent enzyme immunoassay (CLIA), and affinity column-mediated immunoassay (ACMIA), compared with an assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the flow injection assay (FIA-MS/MS) was also evaluated to determine whether it could be available as a new method of analysis in tacrolimus therapy. The blood tacrolimus concentrations in samples from liver transplant recipients (n = 102) were measured using MEIA, CLIA, ACMIA, and LC-MS/MS. Additional blood samples from liver transplant recipients (n = 54) were analyzed using both FIA-MS/MS and LC-MS/MS. Because the assay performance and characteristics of MEIA, CLIA, ACMIA, and FIA-MS/MS are relatively different, the measured data should be carefully considered depending on the methodology..
18. Mio Kikuchi, Yuki Okuda, Yoshihide Ueda, Yuki Nishioka, Miwa Uesugi, Emina Hashimoto, Tamotsu Hashimoto, Tomoki Kawai, Sachiyo Hashi, Haruka Shinke, Tomohiro Omura, Atsushi Yonezawa, Takashi Ito, Yasuhiro Fujimoto, Toshimi Kaido, Tsutomu Chiba, Shinji Uemoto, Kazuo Matsubara, Satohiro Masuda, Successful Telaprevir Treatment in Combination of Cyclosporine against Recurrence of Hepatitis C in the Japanese Liver Transplant Patients, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 37, 3, 417-423, 2014.03, Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150-200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24-0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection..
19. Eriko Sato, Sachiyo Hashi, Risa Taniguchi, Ikuko Yano, Kazuo Matsubara, Eri Ogawa, Atsushi Yoshizawa, Shinya Okamoto, Shinji Uemoto, Satohiro Masuda, Effectiveness of everolimus in combination with cyclosporine as treatment for chronic rejection in a pediatric patient undergoing liver transplantation, Jp J Ther Drug Monitor, 31, 1, 1-5, 2014.02, Everolimus has been approved as an immunosuppressant for heart and kidney transplantation in Japan, but its clinical use in infants has been very limited. We report the effective introduction of everolimus in combination with cyclosporine as treatment for chronic rejection in an 8-month-old girl who underwent living-donor liver transplantation (LDLT) for fulminant hepatitis. Oral tacrolimus was administered (0.5 mg every 12 h) from postoperative day (POD) 1, with the dose adjustments based on trough concentrations. On POD 60, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bil) were 120 U/L, 145 U/L, and 10.8 mg/dL, respectively, and chronic rejection was diagnosed by using pathologic examination. High-dose steroid pulse therapy decreased the AST and ALT levels, but the T-Bil level did not decrease until 11 days after the start of pulse therapy. We then substituted tacrolimus with a combination of cyclosporine (25 mg every 12 h) and everolimus (0.5 mg every 12 h). The dosages were adjusted based on the target trough concentrations of everolimus and cyclosporine (approximately 12-13 ng/mL and 180 ng/mL, respectively). Pharmacokinetic analysis showed the clearance for everolimus to be 0.147 L/hr/kg and the volume of distribution to be 12.6 L/kg. Thereafter, the serum level of T-Bil decreased to 3.0 mg/dL and pathologic examination showed amelioration of the chronic rejection. These results suggest that everolimus therapy in combination with cyclosporine is an effective treatment option for chronic rejection after liver transplantation..
20. Keiko Hosohata, Miwa Uesugi, Sachiyo Hashi, Mio Hosokawa, Ken-ichi Inui, Kazuo Matsubara, Kohei Ogawa, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda, Association between CYP3A5 Genotypes in Graft Liver and Increase in Tacrolimus Biotransformation from Steroid Treatment in Living-donor Liver Transplant Patients, DRUG METABOLISM AND PHARMACOKINETICS, 10.2133/dmpk.DMPK-13-RG-060, 29, 1, 83-89, 2014.02, We retrospectively examined whether cytochrome P450 (CYP) 3A5 genotypes are associated with high-dose steroid pulse treatment-induced functional gain of tacrolimus biotransformation in living-donor liver transplant patients. Concentrations of tacrolimus and its 3 primary metabolites, 13-O-demethyl tacrolimus (M-I), 31-O-demethyl tacrolimus (M-II), and 15-O-demethyl tacrolimus (M-III), were measured in trough blood samples from 18 liver transplant patients, by liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS). In patients engrafted with a CYP3A5*1-carrying liver but not with a CYP3A5*3/*3-carrying liver, the concentration/dose ratio of tacrolimus significantly reduced after therapy, while ratios of M-I/tacrolimus, M-II/tacrolimus, and M-III/tacrolimus were significantly higher after therapy than before (p = 0.032, p = 0.023, and p = 0.0078, respectively). After steroid pulse therapy, the concentration of tacrolimus measured by immunoassay was significantly higher than that measured by LC-MS/MS in patients engrafted with a CYP3A5*1-carrying liver, but not those engrafted with a CYP3A5*3/*3-carrying liver. This suggests that the increased ratio of tacrolimus metabolites/tacrolimus can be explained by induction of CYP3A5 via high-dose steroid pulse therapy. Further, the concentrations of tacrolimus measured by the immunoassays were overestimated, partly because of cross-reactivity of the monoclonal antibody they incorporated to detect tacrolimus, with the increased metabolites in patients with a CYP3A5*1-carrying graft liver..
21. Miwa Uesugi, Mio Hosokawa, Haruka Shinke, Emina Hashimoto, Tamotsu Takahashi, Tomoki Kawai, Kazuo Matsubara, Kohei Ogawa, Yasuhiro Fujimoto, Shinya Okamoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda, Influence of Cytochrome P450 (CYP) 3A4*1G Polymorphism on the Pharmacokinetics of Tacrolimus, Probability of Acute Cellular Rejection, and mRNA Expression Level of CYP3A5 Rather than CYP3A4 in Living-Donor Liver Transplant Patients, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 36, 11, 1814-1821, 2013.11, Association between cytochrome P450 (CYP) 3A4*1G genotype of donors (n=412) and/or recipients (n=410), and the pharmacokinetics of tacrolimus and the risk of acute cellular rejection was examined in Japanese living-donor liver transplant patients between 2004 and 2011. The concentration/dose (C/D) ratio of tacrolimus in patients carrying graft liver with CYP3A4*1/*1 was significantly higher during 7 d after surgery than in that with CYP3A4*1/*1G (214 vs. 157 [ng/mL]/[mg/kg/day], p<0.01). After postoperative day 8, no significant difference was observed among CYP3A4*1G genotypes in the graft liver. However, the C/D ratio in CYP3A4*1/*1 of the intestine was significantly higher than that in CYP3A4*1G/*1G for 5 weeks after surgery (postoperative days 1-14; p<0.001, postoperative days 15-35; p<0.01). During postoperative days 14 and 26, acute cellular rejection incidences tended to be lower in the patients with graft liver carrying the CYP3A4*1/*1 allele than in the patients carrying CYP3A4*1G allele (8.7% vs. 14.6%, p=0.0973). However, CYP3A4*1G in the intestine had almost no effect on the incidence of rejection (9.9% in CYP3A4*1/*1 vs. 12.5% in CYP3A4*1G allele, p=0.4824). CYP3A4*1G was significantly related to mRNA expression of CYP3A5 rather than of CYP3A4 in the graft liver and intestine and was strongly linked with the CYP3A5*1. Thus, we elucidated that CYP3A4*1G genotype in the intestine was an important indicator of the pharmacokinetics of tacrolimus, whereas this genotype in the graft liver tended to influence the frequency of acute cellular rejection after transplantation..
22. Haruka Shinke, Sachiyo Hashi, Risa Kinoshita, Risa Taniguchi, Mitsuhiro Sugimoto, Kazuo Matsubara, Eri Ogawa, Mari Sonoda, Narito Takada, Atsushi Yoshizawa, Kohei Ogawa, Shinya Okamoto, Shinji Uemoto, Satohiro Masuda, Effectiveness of Sirolimus in Combination with Cyclosporine against Chronic Rejection in a Pediatric Liver Transplant Patient, BIOLOGICAL & PHARMACEUTICAL BULLETIN, 36, 7, 1221-1225, 2013.07, The patient is a 3-year-old boy who received living-donor liver transplantation (LDLT) for hepatoblastoma, with his mother as the donor. Oral tacrolimus was started at a dose of 0.3 mg every 12 h from day 1, with the dosage adjusted on the basis of trough concentrations. The levels of aspartate aminotransferase (AST), alanine transferase (ALT), and total bilirubin (T-bil) were 110 U/L, 182 U/L, and 12.6 mg/dL, respectively, when chronic rejection (CR) was pathologically diagnosed. Then, sirolimus at a dose of 1.0 mg/day was added to the tacrolimus-based regimen. The T-bil level rapidly decreased to 5.4 mg/dL, without changes in AST and ALT. Because the intracellular receptor of sirolimus and tacrolimus is FK506-binding protein 12, we switched tacrolimus to cyclosporine at a dose of 60 mg/day to avoid competitive inhibition between these 2 drugs. The target trough concentration of sirolimus and cyclosporine was set to around 15 ng/mL and 180 ng/mL, respectively. The concentration/dose ratio of sirolimus was significantly correlated with the blood cyclosporine level (r = 0.5293, p < 0.05), suggesting the pharmacokinetic interaction between these 2 drugs. Thereafter, the levels of AST and ALT as well as the T-bil were successfully decreased to 73 U/L, 83 U/L, and 3.0 mg/dL, respectively. These results suggest that sirolimus therapy in combination with cyclosporine may be an effective treatment against CR after liver transplantation..
23. Kumiko Nishihara, Satohiro Masuda, Haruka Shinke, Aiko Ozawa, Takaharu Ichimura, Atsushi Yonezawa, Shunsaku Nakagawa, Ken-ichi Inui, Joseph V Bonventre, Kazuo Matsubara, Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity, BIOCHEMICAL PHARMACOLOGY, 10.1016/j.bcp.2012.12.019, 85, 4, 570-582, 2013.02, Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity. Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney. Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased. Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration. Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium. Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels. Urinary levels of KIM-1 also increased 3-fold after cisplatin administration. In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment. These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury..
主要総説, 論評, 解説, 書評, 報告書等
1. 池末 裕明, 増田 智先, 【臨床の疑問に答えるがん薬物療法アップデート】 (第1章)がん治療に関わるすべての薬剤師が知っておきたいこと がん薬物療法の基本, 薬事, 58(2)197-206, 2016.01, がん治療全体を理解し、個々の患者に行われるがん薬物療法の目的を理解する。さまざまなバイオマーカーが明らかになり、これに基づく個別化医療が進展している。がん薬物療法の効果を最大限に引き出すには、エビデンスをもとに標準治療を行い、適切な支持療法により副作用に対応する。薬剤師は、レジメン管理に基づく処方システムや、医療従事者を抗がん薬曝露から守る体制を整備するなど重要な役割を担う。患者個々の全身状態や併用薬、副作用、服薬状況などを考慮し、きめ細かく対応する。.
2. 梶原 望渡, 増田 智先, 【臨床の疑問に答える がん薬物療法アップデート】 (第3章)すべての薬剤師が知っておきたい抗がん薬の薬物動態 抗がん薬とトランスポーター, 薬事, 58(2)393-397, 2016.01, トランスポーターは抗がん薬の体内動態を制御している。トランスポーターは抗がん薬耐性の原因の一つである。トランスポーターの阻害薬は抗がん薬の治療効果を増強する可能性をもつ。トランスポーターの遺伝子多型の情報は、抗がん薬の副作用回避に役立つと期待されている。.
3. 増田 智先, 【移植医学の進歩と病理の役割】 移植免疫の基礎 免疫抑制薬の血中濃度モニタリング, 病理と臨床, 34(2)139-144, 2016.02.
4. 増田 智先, Clinical nephrology E.腎不全(AKI,CKD,移植,透析含む)1.臓器移植におけるmTOR阻害薬の可能性, Annual Review 腎臓 , 2016(-)175-182, 2016.01.
5. Shipkova M, Hesselink DA, Holt DW, Billaud EM, van Gelder T, Kunicki PK, Brunet M, Budde K, Barten MJ, De Simone P, Wieland E, Lopez OM, 増田 智先, Seger C, Picard N, Oellerich M, Langman LJ, Wallemacq P, Morris RG, Therapeutic Drug Monitoring of Everolimus: A Consensus Report. , Therapeutic drug monitoring, 38(2)143-69, 2016.04.
6. 梶原 望渡, 増田 智先, トランスポーターがかかわる薬物間相互作用, 日本病院薬剤師会雑誌, 51(8)967-970, 2015.08.
7. 梶原 望渡, 増田 智先, 【薬剤トランスポーター研究の最新動向と化学療法剤の動態】 腎臓のトランスポーターと化学療法剤, 化学療法の領域, 31(3)394-398, 2015.02, 腎臓の近位尿細管にはイオン性化合物の体外排除系として有機カチオン輸送系および有機アニオン輸送系が備わっており、これらは構造的に多様な薬物など異物の尿中排泄、すなわち血中から尿細管上皮細胞内への取り込み、そして尿細管上皮細胞から尿細管管腔への分泌という方向選択的な経細胞輸送を媒介している。薬物による腎障害発現のメカニズムのひとつとして、尿細管上皮細胞への蓄積がある。このような場合は、尿細管上皮細胞への取り込みを防ぎ、排泄を促すことが腎障害の予防につながる。(著者抄録).
8. 増田 智先, 本間 真人, 竹内 裕紀, 葛谷 孝文, 内藤 隆文, 村木 優一, 岡田 賢二, 谷川原 祐介, 佐藤 滋, 原田 浩, 渡井 至彦, 鳴海 俊治, 三浦 昌明, 新岡 丈典, 湯沢 賢治, 高原 史郎, 日本TDM学会免疫抑制薬TDM標準化ガイドライン策定委員会, 日本移植学会免疫抑制薬TDM標準化ガイドライン策定委員会, 免疫抑制薬tdm標準化ガイドライン2014の策定 Statements, TDM研究, 32 (3)143-159, 2015.09.
9. 増田 智先, 上杉 美和, 新家 遥, 菊池 実緒, 上本 伸二, 松原 和夫, 遺伝子多型・発現情報の肝移植後個別化免疫抑制療法への活用に関する研究, 臨床薬理, 46 (1)43-49, 2015.01.
10. 増田 智先, 【C型肝炎 薬物治療の最前線と求められる多角的視点】 押さえておきたい!C型肝炎治療における薬物動態学的視点 生体肝移植患者への個別化薬物投与, 薬局, 66 (13)3183-3186, 2015.12, <Key Points>生体肝移植後の解毒能は日々刻々と変化する。術後管理は免疫抑制療法に加えて感染症の予防も重要である。CYP3A5の遺伝子多型情報はタクロリムスの用量調節に有用である。肝移植治療ではドナー由来の肝臓と患者自身由来の小腸の遺伝子型が異なる場合が多いため、双方の組み合わせに注目する。肝硬変に対する移植では術前状態において腎機能低下患者が散見されるため、術後管理は腎機能にも注意が必要である。(著者抄録).
11. 増田 智先, 医薬理研究 TDMに基づくエベロリムスの個別化投与, Organ Biology, 22 (2) 105-110, 2015.07.
12. 増田 智先, 【PPIが果たしてきた役割とこれからへの期待】 薬物動態学的特徴を踏まえたプロトンポンプ阻害薬の選択, クリニシアン, 62 (9-10) 928-934, 2015.10.
13. 三浦 昌明, 増田 智先, タクロリムスのTDMの標準化と精度管理, 今日の移植, 28 (2) 184-190, 2015.03, 国内には体外診断用医薬品として四つのイムノアッセイ法(CLIA法、ACMIA法、EMIT法、ECLIA法)と、その他ELISA法が存在する。移植維持期においては、タクロリムスのターゲットトラフ濃度を3.0~5.0ng/mLと低く設定されており、この低濃度領域をいかに正確に測定できるかが各機器に求められる。定量可能な最低値(実効感度、limit of quantification)がすぐれているのは、ECLIA法であり、精度(precision)はECLIA法とCLIA法ですぐれている。また、正確度(accuracy)は、ACMIA法がすぐれている。移植患者の長期生着へは、測定機器の特徴を理解し、定期的な精度管理が求められる。(著者抄録).
14. 増田 智先, 医師と薬剤師が共有すべき薬の新知識(serial 6) 移植免疫療法における薬物トランスポーターの役割, Organ Biology, 20 (1) 29-35, 2013.01, [URL].
主要学会発表等
1. 増田 智先, 免疫抑制薬血中濃度測定QCワークショップ報告, 第51回日本臨床腎移植学会, 2018.02.
2. 増田 智先, TDMを活用した免疫抑制薬の個別化投与設計, 近畿薬剤師合同学術大会2018, 2018.02.
3. 増田 智先, がん薬物治療における「慎重投与例」への対応, 第38回日本臨床薬理学会学術総会, 2017.12.
4. 増田 智先, エベロリムス(含カルシニューリン阻害薬:心臓移植), 第27回日本医療薬学会年会, 2017.11.
5. 増田 智先, 臓器移植後個別化免疫抑制療法の実施における薬剤師の役割, 第53回 移植学会総会, 2017.09.
6. 増田 智先, 薬物による腎障害発現のメカニズム, 医療薬学フォーラム 2017/第25回クリニカルファーマシーシンポジウム, 2017.07.
7. 増田 智先, 検査値を活用した処方修正の提案, 平成29年度 東京薬科大学卒後教育講座(春季), 2017.05.
8. 増田 智先, 免疫抑制薬のTDM:個体間変動と個体内変動, 第46回洞薬会 学術講演会, 2017.04.
9. 増田 智先, 免疫抑制薬血中濃度測定の 全国サーベイ事業結果報告, 第50回 日本臨床腎移植学会, 2017.02.
10. 増田 智先, 感染症治療薬の使い方: 薬物動態や相互作用に着目して, 第19回 感染症 Case Conference, 2016.12.
11. 増田 智先, 臓器移植医療における免疫抑制薬のTDM, 第56回 日本臨床化学会 年次学術集会, 2016.12.
12. 増田 智先, 肝移植患者への免疫抑制薬の使用における効果、副作用、個人差, 「国内初の、肝臓移植を担う高度医療人養成フロジェクト(SNUC-LT)」第6回学術講演会 , 2016.11.
13. 増田 智先, 移植医療における免疫抑制薬のTDM, 第19回 千葉TDMセミナー, 2016.10.
14. 増田 智先, 梶原 望渡, 渡邊 裕之, がん薬物治療における腎障害の尿中バイオマーカー(Urinary biomarkers of acute kidney injury in anti-cancer drug treatment), 第14回日本臨床腫瘍学会学術集会, 2016.07.
15. 増田 智先, 薬毒物による腎障害検出のための尿中バイオマーカーの探索, 医療薬学フォーラム2016/第24回クリニカルファーマシーシンポジウム, 2016.06.
16. 増田 智先, 臓器移植医療における免疫抑制剤のTDM, 第33回日本TDM学会・学術大会, 2016.05.
17. 増田 智先, 金谷 朗子, 武田 真樹, 辻 敏和, 渡邊 裕之, 医療現場における使用薬剤の変遷と 今後の展望, 日本薬剤学会 第31年会, 2016.05.
18. 増田 智先, 免疫抑制剤TDM標準化 ガイドラインについて, シーメンス免疫抑制剤TDM講演会, 2016.04.
19. Satohiro Masuda, Urinary biomarker for drug-induced nephrotoxicity, Predictive Safety Testing Consortium (PSTC) Japan Safety Biomarker Conference, 2017.02.
20. Hiroyuki Watanabe, Toshihiro Irisa, Koujiro Hata, Kazue Nakashima, Satohiro Masuda, Evaluation of the preparation precision of anticancer drugs by the Cancer Drug Compounding Assist System, FIP World Congress, 2016.09.
21. Hiroaki Ikesue, Hiroyuki Watanabe, Satohiro Masuda, Role of pharmacists in the safe and efficient care of patients receiving cancer treatment, FIP World Congress, 2016.09.
22. Satohiro Masuda, The standardization guideline and quality control surveillance in TDM of immunosuppressants in Japan, 2016 IATDMCT Regional Meeting, 2016.08.
23. Kojiro Hata, Hiroaki Ikesue, Shunichi Ohata, Hiroyuki Watanabe, Satohiro Masuda, Association between zoledronic acid-related kidney injury and concomitant administration of hydrophilic rather than lipophilic statins in cancer patients, 2015 Midyear Clinical Meeting and Exhibition, 50th ASHP, 2015.12.
24. Kimitaka Suetsugu, Hiroaki Ikesue, Mayako Uchida, Takahisa Yano, Hiroyuki Watanabe, Moto Kajiwara, Takehiro Kawashiri, Takaaki Yamada, Takeshi Miyamoto, Masato Shiratsuchi, Nobuaki Egashira, Satohiro Masuda, Analysis of the variable factors in the blood tacrolimus concentration during the switch from continuous intraveneous infusion to oral administration after allogeneic hematopoietic stem cell transplantation
, 14th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology, 2015.10.
25. M. Kajiwara, Y. Tamura, H. Shinke, S. Nakagawa, T. Yano, K. Matsubara, Satohiro Masuda, Gene expression analysis of isolated proximal tubules in rat model of tacrolimus-induced chronic kidney disease, Urine Omics & 2nd International Caparica Conference In Translational, 2015.09.
26. Satohiro Masuda, M. Kajiwara, A Tsuchimoto, H. Shinke, M. Uesugi, K. Matsubara, Identification of a useful biomarker for tacrolimus-induced nephrotoxicity in liver transplant patients, Urine Omics & 2nd International Caparica Conference In Translational, 2015.09.
27. Moto Kajiwara, Satohiro Masuda, Critical role of renal H+/organic cation antiporter (multidrug and toxin extrusion) in natriuresis as a dopamine transporter, BioMedical Transporters Conference 2015, 2015.08.
28. Satohiro Masuda, Role of OCT2/MATEs interplay in drug-induced nephrontoxicity, BioMedical Transporters Conference 2015, 2015.08.
29. 増田 智先, TDM領域におけるLC-MS/MS活用 への期待, 第7回 JBF シンポジウム, 2016.03.
30. 増田 智先, 免疫抑制薬TDM標準化ガイドラインの改訂版に向けて Toward New Edition of Japanese ISD-GL
, 第2回 免疫抑制薬TDMセミナー, 2016.02,
.
31. 増田 智先, 薬剤師の立場から 抗真菌薬治療における留意すべき薬物相互作用, 第31回 日本環境感染学会総会・学術集会, 2016.02.
32. 増田 智先, カルシニューリン阻害薬:肝移植領域, 第25回 日本医療薬学会年会, 2015.11.
33. 増田 智先, 薬物性腎障害の非侵襲尿中バイオマーカー, 第25回 日本医療薬学会年会, 2015.11.
34. 増田 智先, "Impact of renal system mediating detoxification and onco-nephrology
(がん化学療法における腎異物排泄機構の重要性)"

, 第30回日本薬物動態学会, 2015.11.
35. 増田 智先, 免疫抑制剤の血中濃度測定精度管理の 重要性とTDMに関する最新知見, 第51回 日本移植学会, 2015.10.
36. 増田 智先, 創薬・育薬の標的としての トランスポーター, 第29回 京都腎臓セミナー, 2015.09.
37. 増田 智先, 個人差とさじ加減, 平成27年度 県民健康づくりセミナー, 2015.09.
38. 増田 智先, 薬物治療に関わる腎薬物トランスポーターの役割, 第7回 あきた腎疾患 トータルマネジメントセミナー, 2015.08.
39. 増田 智先, 急性腎障害の尿中非侵襲バイオマーカー, 第1回 日本医薬品安全性学会学術大会, 2015.07.
40. 増田 智先, 白金系抗がん薬による毒性発現機序の解明と回避法の探索, 第32回日本TDM学会・学術大会, 2015.05.
41. 増田 智先, 臓器移植領域における エベロリムスのTDM, 第32回日本TDM学会・学術大会 , 2015.05.
42. 増田 智先, 免疫抑制薬TDM標準化 ガイドライン, 第64回日本医学検査学会, 2015.05.
43. Moto Kajiwara, Tsuyoshi Ban, Yuki Hanada, Kazuo Matsubara, Satohiro Masuda, Multidrug and toxin extrusion transporters play a key role in natriuresis as a dopamine transporter, EXPERIMENTAL BIOLOGY 2015, 2015.03.
44. Takahisa Yano • Yuya Sakamoto • Yuki Hanada • Aki Takeshita • Fumika Inagaki • Nobuaki Egashira • Satohiro Masuda, Vancomycin induced renal tubular cell injury by reactive oxygen species generation and mitochondrial dysfunction, EXPERIMENTAL BIOLOGY 2015, 2015.03.
45. 増田智先, 腎機能低下患者における抗がん薬の臨床薬理, Onco-Nephrology Forum 第2回講演会, 2015.03.
46. 増田智先, 感染治療におけるTDMの活用, 第7回 福岡県病院薬剤師会学術大会 第25回 感染制御研修会, 2015.03.
47. 増田智先, 腎臓の有機イオントランスポーター: 創薬、機能評価、毒性発現とバイオマーカー, 大分県病院薬剤師会 3月例会, 2015.03.
48. 増田智先, 免疫抑制薬の測定法について その違いを知る, 第3回日本移植学会スプリングセミナー, 2015.03.
49. 増田智先, 免疫抑制薬TDMの現状と国内ガイドライン, 第1回免疫抑制薬とTDMセミナー, 2015.02.
50. 増田智先, 薬物の腎挙動に関わるトランスポーター, 第35回 日本臨床薬理学会年会学術総会, 2014.12.
51. 増田智先, エベロリムスのTDMによる個別投与, 第41回 臓器保存生物医学会, 2014.11.
52. 増田智先, TDMを活用した薬物治療の個別化にむけて, 第76回九州山口薬学大会, 2014.11.
53. 増田智先, CKDにおける腎薬物トランスポーターの機能変動, 第76回九州山口薬学大会, 2014.11.
54. Haruka Shinke, Yuka Tamura, Shunsuke Fujita, Shunsaku Nakagawa, Takahisa Yano, Kazuo Matsubara, Satohiro Masuda, Gene expression analysis of tacrolimus-induced tubulointerstitial fibrosis after ischemia/reperfusion injury, ASN Kidney Week 2013 Annual Meeting, 2014.11.
55. 増田智先, 腎臓における薬物の挙動と トランスポーター, 第3回 くすりと糖尿病学会, 2014.11.
56. 増田智先、奥田有紀、西岡由貴、菊池実緒、上杉美和、端 幸代、中川俊作、松原和夫、上田佳秀、千葉 勉、海道利実、上本伸二, 肝移植後C型肝炎最年少例におけるテラプレビルとシクロスポリンとの相互作用, 第24回日本医療薬学会年会, 2014.09.
57. IATDMCT ISD committee, Concensus meeting in everolimus TMD methodology, IATDMCT ISD meeting, 2014.09.
58. 増田智先, 白金形抗がん薬による毒性発現 メカニズムの解明, 広島県病院薬剤師会 呉支部研修会 がん薬物療法認定薬剤師講習会, 2014.09.
59. 増田智先, 臨床薬剤業務の今後の展開について, PU研究会2014 (Pharmacy Of University 2014), 2014.09.
60. Satohiro masuda, Molecular markers-based dosage adjustment of tacrolimus in liver transplant patients, 2014 FIP World Congress of Pharmacy & Pharmaceutical Sciences, 2014.09.
61. 増田智先, mTOR阻害薬の可能性, 第39回西日本薬剤学研究会, 2014.08.
62. 増田智先, カルシニューリン阻害薬の臨床薬理ー個別化投与設計法の確立を目指してー, 生体機能と創薬シンポジウム2014, 2014.08.
63. 増田智先, 腎機能低下のバイオマーカー:探索から臨床応用にむけて, 第7回福岡腎と薬剤研究会, 2014.08.
64. 増田智先, 潰瘍性大腸炎治療薬「メサラジン製剤」のDDSとその有効性, 第30回日本DDS学会学術集会, 2014.07.
65. 増田智先, 日常TDMにおけるLC-MS/MSの有用性, AB SCIEX LC/MS ユーザーズミーティング 2014, 2014.07.
66. 増田智先, 免疫抑制剤TDMガイドラインの策定, 第32回日本肝移植研究会, 2014.07.
67. 内田まやこ 渡邊裕之 池末裕明 江頭伸昭 増田智先, 血液がん化学療法における医師と協働した薬剤師による後ろ向き臨床研究, 医療薬学フォーラム2014/第22回クリニカルファーマシーシンポジウム, 2014.06.
68. 増田智先, TDM分析のトピックス:LC/MS/MS法 〜事例紹介〜, 第21回クロマトグラフィーシンポジウム, 2014.06.
69. 増田智先, 免疫抑制薬TDM標準化ガイドライン の策定を受けて, 第31回日本TDM学会・学術大会, 2014.05.
70. 矢野貴久 山田孝明 川尻雄大 牛尾聡一郎 江頭伸昭 増田智先, タクロリムスおよびシクロスポリン血中濃度測定における電気化学免疫測定法(ECLIA法)の特性の検討, 第31回日本TDM学会・学術集会, 2014.05.
71. 牛尾聡一郎 矢野貴久 小澤奈々 小野佑子 江頭伸昭 増田智先, LC-MS/MS法を用いた免疫抑制薬およびその代謝物の同時測定法の構築, 第31回日本TDM学会・学術集会, 2014.05.
72. 山田孝明 中村雅子 窪田敏夫 落合正行 矢野貴久 川尻雄大 村岡香代子 江頭伸昭 原寿郎 増田智先, 新生児におけるテイコプラニン血中濃度と有害反応発現の関連性に関する検討, 第31回日本TDM学会・学術集会, 2014.05.
73. 増田智先, 薬物治療の標的としての 腎トランスポーター, 第84回 福岡県筑後地区病院薬剤師研修会, 2014.05.
74. 増田智先, 腎臓のトランスポーターを標的とした 薬物治療, 腎臓熊本県病院薬剤師会講演会, 2014.05.
75. 増田智先, 肝臓移植治療における薬剤師の役割, 平成26年 度九州大学大学院薬学研究院公開講座, 2014.05.
76. 増田智先, 免疫抑制薬のTDM: 薬学的側面からの介入の可能性, 第2回 大阪臨床薬理セミナー, 2014.05.
77. Kawahiri T Tsutsumi K Ushio S Egashira N Masuda S, Prophylactic effect of calcium channel blockers against oxaliplatin-induced acute peripheral neuropathy, Experimental Biology 2014, 2014.04.
78. Ushio S Mitsuyasu S Masuguchi K Ozawa N Ono Y Kawashiri T Egashira N Masuda S, Assosciation between decreased expression of GLT-1 derived spinal glutamate accumulation and oxaliplatin-induced mechanical allodynia, Experimental Biology 2014, 2014.04.
79. 増田智先, 臓器移植におけるmTOR阻害薬の可能性, 第11回 Kidney Transplant Fraternity by Urologist, 2014.04.
80. 増田智先, 免疫抑制剤のTDM-GLについて, 第47回日本臨床腎移植学会, 2014.03.
81. 増田智先, 感染制御認定薬剤師 認定のための ポイント, 第1回 福岡感染制御薬剤師セミナー, 2014.03.
82. 増田智先, タクロリムスのTDM: TDMガイドラインの概要と測定法の注意点について, 第20回福岡腎移植セミナー, 2014.02.
83. 増田智先, 尿細管薬物輸送機構と薬物による腎障害, 第24回北部九州腎と薬剤研究会, 2014.01.
84. 梶原望渡、松原和夫、増田智先, 腎臓のトランスポーターの重要性, 第2回日本くすりと糖尿病学会学術集会, 2013.11.
85. 増田智先, 移植医療における免疫抑制療法と副作用対策, 第7回日本薬局学会総会, 2013.11.
86. Moto Kajiwara, Tsuyoshi Ban, Kazuo Matsubara, Satohiro Masuda, Role of tubular luminal H+/organic cation transporter, MATE, in natriuresis as a dopamine transporter, 第46回米国腎臓学会(ASN), 2013.11.
87. Haruka Shinke, Yasuaki Ikemi, Masami Tadehara, Kazuo Matsubara, Yousuke Togashi, Young Hak Kim, Michiaki Mishima, Takaharu Ichimura, Joseph V. Bonventre, Satohiro Masuda., Kidney injury molecule-1 and monocyte chemotactic protein-1 as sensitive biomarkers for detecting cisplatin-induced nephrotoxicity in patients with lung cancer., 第46回米国腎臓学会(ASN), 2013.11.
88. Haruka Shinke, Ayami Tsuchimoto, Venkata S Sabbisetti, Miwa Uesugi, Emina Hashimoto, Kazuo Matsubara, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Motoko Yanagita, Takaharu Ichimura, Joseph V. Bonventre, Satohiro Masuda, Urinary kidney injury molecule-1 (KIM-1) levels immediately after surgery predict the development of tacrolimus-related chronic kidney disease in liver transplantation recipients, 第46回米国腎臓学会(ASN), 2013.11.
89. Miwa Uesugi, Satohiro Masuda, Haruka Shinke, Yuki Nishioka, Kazuo Matsubara, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Influence of the cytochrome P450 3A5*3 genotype in a graft liver on the occurrence of acute cellular rejection after living-donor liver transplantation, 第64回米国肝臓学会(AASLD), 2013.11.
90. Haruka Shinke, Ayami Tsuchimoto, Miwa Uesugi, Kazuo Matsubara, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Motoko Yanagita, Satohiro Masuda, Urinary neutrophil gelatinase-associated lipocalin as a biomarker for tacrolimus-induced acute kidney injury in recipients of living-donor liver transplantation, 第64回米国肝臓学会(AASLD), 2013.11.
91. Haruka Shinke, Miwa Uesugi, Yuki Okuda, Risa Taniguchi, Kazuo Matsubara, Eri Ogawa, Atsushi Yoshizawa, Shinya Okamoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda, Novel sets of genes are correlated with acute cellular rejection after pediatric living-donor liver transplantation, 第64回米国肝臓学会(AASLD), 2013.11.
92. 増田智先, 尿中安全性バイオマーカーの探索と臨床応用, 九大別府病院秋の集談会, 2013.10.
93. Sachiyo Hashi, Mai Shibata, Satohiro Masuda, Kazuo Matsubara, Masako Kinoshita, Riki Matsumoto, Akio Ikeda, Ryosuke Takahashi, Ikuko Yano, Impact of CYP2C19 polymorphisms on pharmacokinetics and pharmacodynamics of low-dose clobazam therapy in Japanese patients with epilepsy, 第13回国際TDM学会(IATDMCT), 2013.09.
94. Satohiro Masuda, Pharmacogenomics for Adequate Dosage Regimen of Immunusuppressants in Liver Transplant Patients, 第13回国際TDM学会(IATDMCT), 2013.09.
95. 増田 智先, 三浦 昌朋, 江川 裕人, 湯沢 賢治, 松原 和夫, タクロリムスの血中濃度測定の精度管理と評価 2013, 日本移植学会, 2013.09.
96. Sachiyo Hashi, Satohiro Masuda, Mio Kikuchi, Miwa Uesugi, Toshimi Kaido, Shinji Uemoto, Ikuko Yano, Kazuo Matsubara, Assessment of four methodologies (MEIA, CLIA, ACMIA, EMIT) for measuring tacrolimus blood concentration in clinical practice, 第13回アジア移植学会(AST), 2013.09.
97. Miwa Uesugi, Mio Hosokawa, Haruka Shinke, Kazuo Matsubara, Kohei Ogawa, Yasuhiro Fujimoto, Toshimi Kaido, Shinji Uemoto, Satohiro Masuda, Effect of cytochrome P450 3A5*3 polymorphism of the graft liver rather than native intestine on occurrence of acute cellular rejection in patients receiving living-donor liver transplantation, 第13回アジア移植学会(AST), 2013.09.
98. 増田智先, 免疫抑制剤のTDM-GLについて, 第47回日本臨床腎移植学会, 2013.03.
99. 牛尾聡一郎 光安正平 小澤奈々 小野佑子 川尻雄大 増田智先 大石了三 江頭伸昭, オキサリプラチン誘発機械的アロディニアにおける脊髄内グルタミン酸の関与, 第87回 日本薬理学会.
100. 藤田隼輔 牛尾聡一郎 益口賢 小澤奈々 小野佑子 馬場美咲 川尻雄大 増田智先 大石了三 江頭伸昭, オキサリプラチン誘発末梢神経障害に対するエキセナチドの効果, 第87回 日本薬理学会.
101. 南 晴奈 三嶋 一登 永田 健一郎 入佐 俊弘 江頭 伸昭 増田 智先, メトトレキサート大量療法での1000 mg製剤規格への変更における調製時間、職業性曝露リスクおよび経済効果に関する検討, 日本薬学会第134年会.
102. 大畠俊一 辻敏和 入佐俊弘 國分千代 金谷朗子 末安正典 川重誠 江頭伸昭 増田智先, 「薬名違い」における調剤過誤と患者影響との関係, 日本薬学会第134年会.
103. 石田 茂 武田真樹 尾川理恵 池末裕明 渡邊裕之 江頭伸昭 増田智先, ICUで使用される注射剤の文献調査に基づく配合変化早見表の開発, 日本薬学会第134年会.
104. 中島貴史 渡邊裕之 手嶋由加 永田健一郎 末次王卓 池末裕明 末安正典 江頭伸昭 増田智先, ゲムシタビンの末梢静脈投与による血管障害のリスク因子解析, 日本薬学会第134年会.
105. 池田 秀優 田島 壮一郎 月野木 祥子 若杉 陽子 グリム 理恵子 國分 千代 末安 正典 江頭 伸昭 増田 智先, 病棟配置麻薬状況把握システムの導入とその取り組み, 日本薬学会第134年会.
106. 坂本裕哉 矢野貴久 花田有希 竹下亜希 大石了三 江頭伸昭 増田智先, バンコマイシン誘発尿細管上皮細胞障害発現における活性酸素種の役割, 日本薬学会第134年会.
107. 山本将大 川尻雄大 堤国章 牛尾聡一郎 要幸典 樋口瞳 白濱雅史 増田智先 江頭伸昭, ボルテゾミブ誘発末梢神経障害の特性と鎮痛薬および鎮痛補助薬の効果, 日本薬学会第134年会.
学会活動
所属学会名
日本薬学会
日本薬物動態学会
日本医療薬学会
日本薬剤学会
日本TDM学会
日本臨床薬理学会
日本腎臓学会
日本移植学会
日本感染症学会
日本臨床腫瘍学会
日本病院薬剤師会
米国臨床薬理学会
米国腎臓病学会
国際腎臓病学会
米国生理学会
米国薬学会
国際TDM学会
米国肝臓病学会
米国病院薬剤師会
学協会役員等への就任
2016.09~2018.03, 日本薬物動態学会, 代議員.
2016.01~2018.12, 日本医療薬学会, 代議員.
2015.01~2018.06, 日本医療薬学会, 広報委員会委員.
2018.06~2019.06, 日本医薬品情報学会, .
2016.01~2018.06, 日本移植学会, 移植関連検査委員会.
2017.06~2018.06, 日本腎臓学会, .
2017.06~2019.06, 日本薬剤学会, .
2009.09~2018.06, 日本薬物動態学会, 評議員.
2014.01~2018.06, 日本薬学会, 医療薬科学部会常任世話人、代議員.
2010.06~2018.06, 日本TDM学会, 評議員.
2014.06~2018.06, 日本TDM学会, 理事.
2010.01~2018.06, 日本臨床薬理学会, 評議員.
2012.01~2018.06, 日本臨床薬理学会, 総務委員.
2013.09~2018.06, International Association of Therapeutic Drug Monitoring and Clinical Toxicology, IATDMCT, member of Immunosuppressive Drugs Committee.
2018.06~2019.06, 日本病院薬剤師会, 感染制御専門薬剤師認定委員.
2018.06~2019.06, 日本病院薬剤師会, 国際交流委員.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2015年度 34    30  68 
受賞
遺伝子多型・発現情報の肝移植後個別化免疫抑制療法への活用に関する研究, 日本臨床薬理学会, 2011.12.
第26回日本臨床薬理学会別府年会 優秀演題ポスター賞受賞, 日本臨床薬理学会, 2005.12.
日本薬学会奨励賞(平成17年度), 日本薬学会, 2005.03.
日本薬物動態学会奨励賞(平成13年度), 日本薬物動態学会, 2001.10.
日本薬学会近畿支部奨励賞(平成10年度), 日本薬学会, 1999.01.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2015年度~2017年度, 基盤研究(B), 代表, 免疫抑制薬の副作用に着目した慢性移植腎症の分子機構解明と非侵襲マーカーの探索.
2014年度~2015年度, 挑戦的萌芽研究, 代表, mTOR阻害薬の非侵襲薬効評価系としての尿中LC3定量評価システムの開発.
日本学術振興会への採択状況(科学研究費補助金以外)
2010年度~2013年度, 最先端・次世代研究開発支援プログラム, 代表, 移植肝障害のバイオマーカー創製.
共同研究、受託研究(競争的資金を除く)の受入状況
2017.04~2019.03, 代表, 抗がん薬調整支援システムの実運用評価等に関する研究.
2017.04~2019.03, 代表, 抗がん薬調製支援システムを用いた自動調製と調製業務の評価等に関する研究
.
2017.09~2018.03, 代表, アーキテクト メソトレキサートの基礎性能評価.
2016.04~2018.03, 代表, 抗がん剤薬調整支援システムの実運用上の評価.
2016.04~2018.03, 代表, 抗がん剤支援システムの開発研究.
2016.10~2017.09, 代表, 抗がん剤曝露調査の新規調査法「ほこりキャッチシート」.
2016.11~2017.12, 代表, フレックスカートリッジ タクロリムス TACに関する総合評価.
2016.09~2016.08, 代表, アーキテクト メソトレキサートの基礎性能評価.
2015.10~2016.03, 代表, フレックスカートリッジ タクロリムス TACに関する総合評価.
2015.10~2016.03, 代表, アーキテクト メソトレキサートの基礎性能評価.
2014.07~2015.06, 代表, 薬物濃度測定法の開発.
2015.07~2016.06, 代表, 薬物濃度測定法の開発.
2014.06~2016.05, 代表, 臨床で有用性の高い薬剤性腎障害バイオマーカーの探索に関する共同研究.
2014.09~2015.12, 代表, タクロリムス血中濃度測定の精度管理に係るデータ収集システム構築・管理業務.
2014.10~2015.12, 代表, アーキテクト メソトレキサートの基礎性能評価.
2014.12~2016.12, 代表, 「エクルーシス試薬シクロスポリン」および「エクルーシス試薬タクロリムス」を用いた特異性に関する性能評価研究.
2014.07~2015.06, 代表, 薬物濃度測定法の開発.
2013.10~2014.05, 代表, 薬物濃度測定法の開発.
2014.03~2016.03, 代表, 抗がん剤支援システムの開発研究.
寄附金の受入状況
2017年度, 杏林製薬株式会社, 臨床薬学研究に対する研究助成(IBD患者における薬剤の粘膜内濃度を解明する).
2017年度, 小野薬品工業株式会社, 臨床薬学研究に対する研究助成.
2017年度, 株式会社ツムラ, 臨床薬学研究に対する研究助成.
2017年度, アボットジャパン株式会社, 臨床薬学研究に対する研究助成.
2017年度, エーザイ株式会社, 臨床薬学研究に対する研究助成.
2017年度, 株式会社ヤクルト, 臨床薬学研究に対する研究助成.
2017年度, 帝人ファーマ株式会社, 臨床薬学研究に対する研究助成
.
2017年度, 武田薬品工業株式会社, 臨床薬学研究に対する研究助成.
2017年度, 第一三共株式会社, 九州大学病院 薬剤部への学術教育研究助成のため.
2017年度, 日本化薬株式会社, 臨床薬学研究に対する研究助成.
2017年度, アステラス製薬株式会社
, 九州大学病院における教育・研究のため
(薬剤部・臨床薬物治療学講座における臓器移植医療領域に関する研究).
2017年度, 大鵬薬品工業株式会社, 臨床薬学研究に対する研究助成
(薬物トランスポーターを中心とした薬物相互作用メカニズム解明).
2017年度, バイエル薬品株式会社, 臨床薬学研究に対する研究助成.
2017年度, 杏林製薬株式会社, 臨床薬学研究に対する研究助成(IBD患者における薬剤の粘膜内濃度を解明する).
2017年度, ファイザー株式会社, 臨床薬学研究に対する研究助成
(循環器疾患に関する研究).
2017年度, 持田製薬株式会社, 免疫抑制薬の個別化投与設計法の確立.
2017年度, 大正富山医薬品株式会社, 臨床薬学研究に対する研究助成
「薬物による腎性浮腫の分子機構解明」.
2017年度, 中外製薬株式会社, 臨床薬学研究に対する研究助成.
2017年度, 大塚製薬株式会社, 慢性腎臓病早期診断の尿中バイオマーカーの探索.
2017年度, 東和薬品株式会社, 医薬品適正使用の研究のため.
2016年度, 持田製薬株式会社, 薬剤性腎障害の分子機構解明.
2016年度, 大塚製薬株式会社, 急性腎不全の尿中バイオマーカーの探索.
2016年度, 東和薬品株式会社, 臨床薬学研究に対する研究助成.
2016年度, 大正富山医薬品株式会社, 臨床薬学研究に対する研究助成.
2016年度, アボットジャパン株式会社, 臨床薬学研究に対する研究助成.
2016年度, エーザイ株式会社, 臨床薬学研究に対する研究助成.
2016年度, ロシュ・ダイアグノスティックス株式会社, 臨床薬学研究に対する研究助成.
2016年度, ファイザー株式会社, 臨床薬学研究に対する研究助成
(循環器系疾患に関する研究).
2016年度, 株式会社ヤクルト, 臨床薬学研究に対する研究助成.
2016年度, アステラス製薬株式会社, 臨床薬学研究に対する研究助成
(薬剤部における移植医療領域に関する研究).
2016年度, 日本イーライリリー株式会社, 臨床薬学研究に対する研究助成
(薬物腎障害検出のための非侵襲バイオマーカーの探索).
2016年度, 一般社団法人日本血液製剤機構, 臨床薬学研究に対する研究助成
(炎症性腸疾患患者における薬物の適正使用法の構築).
2016年度, 田辺三菱製薬株式会社, 臨床薬学研究に対する研究助成
(薬剤性腎障害発現の分子機構解明に基づく非侵襲尿中バイオマーカーの探索).
2016年度, 武田薬品工業株式会社, 臨床薬学研究に対する研究助成
.
2016年度, 大鵬薬品工業株式会社, 臨床薬学研究に対する研究助成
(薬物トランスポーターを中心とした薬物相互作用メカニズムの解明).
2016年度, フェリング・ファーマ株式会社, 臨床薬学研究に対する研究助成.
2016年度, 株式会社ツムラ, 臨床薬学研究に対する研究助成.
2016年度, 帝人ファーマ株式会社, 臨床薬学研究に対する研究助成
(造血幹細胞移植を受けた患者における免疫抑制薬の薬物血中濃度に影響を及ぼす因子に関する臨床検査).
2016年度, 小野薬品工業株式会社, 臨床薬学研究に対する研究助成.
2016年度, 日本化薬株式会社, 臨床薬学研究に対する研究助成.
2015年度, 一般社団法人 九州臨床研究支援センター, 臨床薬学研究に対する研究助成.
2015年度, 持田製薬株式会社, 臨床薬学研究に対する研究助成
(腎性浮腫の分子機構解明).
2015年度, 東和薬品株式会社, 臨床薬学研究に対する研究助成.
2015年度, エーザイ株式会社, 臨床薬学研究に対する研究助成.
2015年度, 中外製薬株式会社, 臨床薬学研究に対する研究助成.
2015年度, アステラス製薬株式会社, 臨床薬学研究に対する研究助成
(薬剤部における移植医療領域に関する研究).
2015年度, 大塚製薬株式会社, 臨床薬学研究に対する研究助成
(薬剤性腎障害の非侵襲バイオマーカーの探索).
2015年度, アボットジャパン株式会社, 臨床薬学研究に対する研究助成
.
2015年度, 協和発酵キリン株式会社, 臨床薬学研究に対する研究助成.
2015年度, 大鵬薬品工業株式会社, 臨床薬学研究に対する研究助成
(薬物トランスポーターを中心とした薬物相互作用メカニズムの解明).
2015年度, 武田薬品工業株式会社, 臨床薬学研究に対する研究助成
(薬剤性腎障害の非侵襲検出を目指した新しい尿中バイオマーカーの探索).
2015年度, 株式会社ヤクルト, 臨床薬学研究に対する研究助成.
2015年度, エーザイ株式会社, 臨床薬学研究に対する研究助成.
2015年度, 科研製薬株式会社, 臨床薬学研究に対する研究助成.
2015年度, 一般社団法人日本血液製剤機構, 臨床薬学研究に対する研究助成
(免疫抑制剤の適正使用法解明).
2015年度, 杏林製薬株式会社, 臨床薬学研究に対する研究助成
(粘膜内濃度測定フォロー).
2015年度, 日本化薬株式会社, 臨床薬学研究に対する研究助成.
2015年度, ノバルティスファーマ株式会社, 臨床薬学研究に対する研究助成
(薬物性腎障害の非侵襲バイオマーカー探索).
2015年度, ファイザー株式会社, 臨床薬学研究に対する研究助成
(循環器系疾患に関する研究).

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。
 
 
九州大学知的財産本部「九州大学Seeds集」