九州大学 研究者情報
論文一覧
廣田 豪(ひろた たけし) データ更新日:2019.06.19

准教授 /  薬学研究院 臨床薬学部門 薬物動態学分野


原著論文
1. Takeshi Hirota, Shota Muraki, Ichiro Ieiri, Clinical Pharmacokinetics of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer, Clinical Pharmacokinetics, 10.1007/s40262-018-0689-7, 58, 4, 403-420, 2019.04, [URL], The identification of anaplastic lymphoma kinase rearrangements in 2–5% of patients with non-small-cell lung cancer led to rapid advances in the clinical development of oral tyrosine kinase inhibitors. Anaplastic lymphoma kinase inhibitors are an effective treatment in preclinical models and patients with anaplastic lymphoma kinase-translocated cancers. Four anaplastic lymphoma kinase inhibitors (crizotinib, ceritinib, alectinib, and brigatinib) have recently been approved. Post-marketing studies provided additional pharmacokinetic information on their pharmacokinetic parameters. The pharmacokinetic properties of approved anaplastic lymphoma kinase inhibitors have been reviewed herein. Findings from additional studies on the effects of drug-metabolizing enzymes, drug transporters, and drug–drug interactions have been incorporated. Crizotinib, ceritinib, and alectinib reach their maximum plasma concentrations after approximately 6 h and brigatinib after 1–4 h. These drugs are primarily metabolized by cytochrome P450 3A with other cytochrome P450 enzymes. They are mainly excreted in the feces, with only a minor fraction being eliminated in urine. Crizotinib, ceritinib, and brigatinib are substrates for the adenosine triphosphate binding-cassette transporter B1, whereas alectinib is not. The different substrate specificities of the transporters play a key role in superior blood–brain barrier penetration by alectinib than by crizotinib and ceritinib. Although the absorption, distribution, and excretion of anaplastic lymphoma kinase inhibitors are regulated by drug transporters, their transporter-mediated pharmacokinetics have not yet been elucidated in detail in patients with non-small-cell lung cancer. Further research to analyze the contribution of drug transporters to the pharmacokinetics of anaplastic lymphoma kinase inhibitors in patients with non-small-cell lung cancer will be helpful for understanding the mechanisms of the inter-individual differences in the pharmacokinetics of anaplastic lymphoma kinase inhibitors..
2. Yushi Kashihara, Yui Terao, Kensaku Yoda, Takeshi Hirota, Toshio Kubota, Miyuki Kimura, Shunji Matsuki, Masaaki Hirakawa, Shin Irie, Ichiro Ieiri, Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation, European Journal of Clinical Pharmacology, 10.1007/s00228-018-2568-4, 75, 3, 351-361, 2019.03, [URL], Background: Magnesium oxide (MgO) is often co-prescribed with L-dopa/carbidopa (LDCD) to improve constipation in Parkinson’s disease patients. The mixing of L-dopa and MgO has been shown to degrade L-dopa; however, there is no interaction study on humans. We proposed mechanisms for the interaction between LDCD and MgO and conducted pharmacokinetic studies on rats and humans. To assess pharmacodynamic changes with the MgO treatment, we applied a model-based meta-analysis (MBMA). Methods: The effects of MgO on the stabilities of L-dopa and carbidopa were evaluated in in vitro studies. We conducted pharmacokinetic interaction studies of MgO and LDCD on rats and healthy volunteers. A clinical study was conducted with an open-label, non-randomized, single-arm, and two-phase study. In MBMA, we constructed a population pharmacokinetic/pharmacodynamic model of L-dopa and predicted the effects of the MgO treatment on the pharmacodynamics of L-dopa. Results: In vitro results suggested that carbidopa was unstable under alkaline pH conditions. Reductions in plasma LDCD concentrations were observed after oral-MgO/oral-LDCD, but not in oral-MgO/i.v.-LDCD treatments in rats, suggesting that the gastrointestinal tract is an interaction site. A healthy volunteer study showed that MgO was also associated with significant decreases of 35.3 and 80.9% in the AUC 0–12 of L-dopa and carbidopa, respectively. A model-based simulation suggested that the MgO treatment was undesirable for the effectiveness of L-dopa. Conclusions: This is the first study to show a clear pharmacokinetic interaction between LDCD and MgO in humans. Further investigations to confirm the effects of MgO on the pharmacodynamics of L-dopa are required..
3. Daiki Mori, Yushi Kashihara, Takashi Yoshikado, Miyuki Kimura, Takeshi Hirota, Shunji Matsuki, Kazuya Maeda, Shin Irie, Ichiro Ieiri, Yuichi Sugiyama, Hiroyuki Kusuhara, Effect of OATP1B1 genotypes on plasma concentrations of endogenous OATP1B1 substrates and drugs, and their association in healthy volunteers, Drug metabolism and pharmacokinetics, 10.1016/j.dmpk.2018.09.003, 34, 1, 78-86, 2019.02, [URL], This study aimed to elucidate the impact of OATP1B1 genotype (*1b/*1b, *1b/*15, and *15/*15) on plasma concentrations of endogenous OATP1B1 substrates. Healthy volunteers with OATP1B1 *1b/*1b (n = 10), *1b/*15 (n = 7), or *15/*15 (n = 2) received oral administration of a cocktail of statins (atorvastatin, pitavastatin, rosuvastatin, and fluvastatin). Mean area under the plasma concentration of atorvastatin, pitavastatin, and rosuvastatin in OATP1B1 *15/*15 were 2.2, 1.7 and 1.58-times greater than the corresponding values in OATP1B1 *1b/*1b, respectively, whereas that of fluvastatin was identical to those in other OATP1B1 genotypes. OATP1B1 *15/*15 also showed higher mean plasma concentrations of OATP1B1 endogenous substrates compared with the other OATP1B1 genotypes, such as coproporphyrin I, glycochenodeoxycholate sulfate (GCDCA-S), lithocholate sulfate (LCA-S), glycolithocholate sulfate (GLCA-S) and taurolithocholate sulfate (TLCA-S), but not total or direct bilirubin, chenodeoxycholate-24-glucuronide, or ω-dicarboxylic long-chain fatty acids. Area under the plasma concentration-time curves of plasma coproporphyrin I and GLCA-S discriminated OATP1B1 genotype *15/*15 from the other genotypes. In combination with previously published clinical studies, these results support the notion that coproporphyrin I, and GLCA-S and GCDCA-S could be a surrogate probe for assessing human in vivo OATP1B1 activities..
4. Hiroyuki Inoue, Yoko Tamaki, Yushi Kashihara, Shota Muraki, Makoto Kakara, Takeshi Hirota, Ichiro Ieiri, Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients
a model-based meta-analysis, British journal of clinical pharmacology, 10.1111/bcp.13807, 85, 2, 393-402, 2019.02, [URL], Aims: The aim of the present study was to quantitate the hypoglycaemic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1r) and sodium glucose cotransporter 2 inhibitors (SGLT2i) as add-on treatments to metformin monotherapy in patients with type 2 diabetes mellitus (T2DM) using a model-based meta-analysis (MBMA). Methods: A systematic literature search of public databases was conducted to develop models that describe the time courses of the fasting plasma glucose (FPG)- and haemoglobin A1c (HbA1c)-lowering effects of three antidiabetic classes using NONMEM 7.3.0. Results: Seventy-six publications were eligible for this study, and 873 FPG and 1086 HbA1c values were collected. We developed a physiological indirect response model that described the time courses of FPG and HbA1c and simulated reductions in these values 90 days after the initiation of add-on treatments. FPG and HbA1c reductions with once weekly exenatide, liraglutide and dulaglutide were greater than those with other drugs. Mean changes from baseline FPG and HbA1c with these drugs were as follows: exenatide (−22.5 and −16.6%), liraglutide (−22.1 and −16.3%), and dulaglutide (−19.3 and −14.3%). The hypoglycaemic effects of DPP-4i and SGLT2i were similar. Conclusions: Once weekly exenatide, liraglutide and dulaglutide provided better hypoglycaemic effects among the antidiabetic drugs analysed. Long-acting GLP-1r appears to be more useful for T2DM patients inadequately controlled with metformin monotherapy..
5. Shunsuke Fujita, Takeshi Hirota, Ryo Sakiyama, Misaki Baba, Ichiro Ieiri, Identification of drug transporters contributing to oxaliplatin-induced peripheral neuropathy, Journal of Neurochemistry, 10.1111/jnc.14607, 148, 3, 373-385, 2019.02, [URL], Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose-limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy. We identified 12 platinum transporters expressed in DRG with real-time PCR, and their transiently overexpressing cells were established. After exposure to oxaliplatin, the accumulation of platinum in these overexpressing cells was evaluated using a coupled plasma mass spectrometer. Octn1/2- and Mate1-expressing cells showed the intracellular accumulation of oxaliplatin. In an animal study, peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg, intravenously, twice a week) to siRNA-injected rats (0.5 nmol, intrathecally, once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA-injected rats developed more severe neuropathy than control rats. These results indicate that Octn1 and Mate1 are involved in platinum accumulation at DRG and oxaliplatin-induced peripheral neuropathy. (Figure presented.)..
6. Yoko Tamaki, Kunio Maema, Makoto Kakara, Masato Fukae, Ryoko Kinoshita, Yushi Kashihara, Shota Muraki, Takeshi Hirota, Ichiro Ieiri, Characterization of changes in HbA1c in patients with and without secondary failure after metformin treatments by a population pharmacodynamic analysis using mixture models, Drug metabolism and pharmacokinetics, 10.1016/j.dmpk.2018.08.002, 33, 6, 264-269, 2018.12, [URL], The objective of the present study was to develop a population pharmacodynamic (PPD) model to describe the glycated hemoglobin (HbA1c)-lowering effects of metformin in type 2 diabetes mellitus patients with and without secondary failure and to characterize changes in HbA1c levels in the two subpopulations using a mixture model. Information on patients was collected retrospectively from electronic medical records. In this study, the mixture model was used to characterize the bimodal effects of metformin. A PPD analysis was performed using NONMEM 7.3.0. A physiological indirect response model, based on 829 HbA1c levels of 69 patients, described the time course for the HbA1c-lowering effects of metformin. Evidence for the different effectiveness of metformin subpopulations was provided using the mixture model. In the final PPD model, the inhibition effect was constant over a study duration in a patient subpopulation without secondary failure. In contrast, the inhibition effect decreased as a function of time after start of metformin treatment in a subpopulation with secondary failure. These results indicated that HbA1c improvements appeared to deteriorate over time in patients with secondary failure. In a PPD analysis of metformin, it was possible to assign patients with secondary failure using the mixture model..
7. Hiroaki Takesue, Takeshi Hirota, Mami Tachimura, Ayane Tokashiki, Ichiro Ieiri, Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells, Molecular Pharmacology, 10.1124/mol.118.111807, 94, 3, 953-962, 2018.09, [URL], Filtered glucose is mostly reabsorbed by sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules. SGLT2 is predominantly expressed in the human kidney. However, the regulatory mechanisms for SGLT2 gene expression in the human kidney remain unclear. We in this work elucidated the transcriptional regulatory mechanisms for the SGLT2 gene by nucleosome occupancy in the SGLT2 promoter region. Expressions of SGLT2 mRNA and protein were markedly weaker in human kidney-derived HK-2 cells than the human kidney. The nucleosome occupancy level in the SGLT2 promoter region was low in the kidney, but high in HK-2 cells. A treatment with a histone deacetylase inhibitor trichostatin A (TSA) decreased nucleosome occupancy in the promoter region and increased SGLT2 expression levels in HK-2 cells. The upregulation of SGLT2 expression by histone acetylation was accompanied by a higher binding frequency of hepatocyte nuclear factor (HNF) 1a, a transcriptional modulator of SGLT2 in the human kidney, to the promoter region. The transfection of a HNF1a expression plasmid into HK-2 cells resulted in the upregulation of SGLT2 mRNA expression in the presence of TSA, but not in the treatment of dimethylsulfoxide as a control. Nucleosome occupancy in the promoter region was markedly higher in the liver and small intestine than the kidney. Our results indicate that tissue-specific nucleosome occupancy plays an important role in the regulation of SGLT2 gene expression via HNF1a binding at the SGLT2 promoter region..
8. Takechi T, Hirota T, Sakai T, Maeda N, Kobayashi D, Ieiri I., Interindividual Differences in the Expression of ATP-Binding Cassette and Solute Carrier Family Transporters in Human Skin: DNA Methylation Regulates Transcriptional Activity of the Human ABCC3 Gene, Drug Metab Dispos, 46, 5, 628-635, 2018.05.
9. Muraki S, Moriki K, Shigematsu S, Fukae M, Kakara M, Yamashita D, Hirota T, Takane H, Shimada M, Hirakawa M, Ieiri I., Population Pharmacodynamic Analysis of Uric Acid-Lowering Effects of Febuxostat Based on Electronic Medical Records in Two Hospitals, JOURNAL OF CLINICAL PHARMACOLOGY, 10.1002/jcph.1023, 58, 3, 304-313, 2018.03.
10. Tanaka T, Hirota T, Ieiri I., Relationship between DNA Methylation in the 5 ' CpG Island of the SLC47A1 (Multidrug and Toxin Extrusion Protein MATE1) Gene and Interindividual Variability in MATE1 Expression in the Human Liver, MOLECULAR PHARMACOLOGY, 10.1124/mol.117.109553, 93, 1, 1-7, 2018.01.
11. Yuji Kashihara, ICHIRO IEIRI, Takashi Yoshikado, Kazuya Maeda, Masato Fukae, Miyuki Kimura, Takeshi Hirota, Shunji Matsuki, Shin Irie, Noritomo Izumi, Hiroyuki Kusuhara, Yuichi Sugiyama, Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP., J Pharm Sci, in press, 2017.03.
12. Takeshi Hirota, Toshihiro Tanaka, Hiroaki Takesue, ICHIRO IEIRI, Epigenetic regulation of drug transporter expression in human tissues., Expert Opin Drug Metab Toxicol, 13, 1, 19-30, 2017.01.
13. Masato Fukae, Yoshimasa Shiraishi, Takeshi Hirota, Yuka Sasaki, Mika Yamahashi, Koichi Takayama, Nakanishi Y, ICHIRO IEIRI, Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer., Cancer Chemother Pharmacol, 78, 5, 1013-1023, 2016.11.
14. Keisuke Gotanda, Takeshi Hirota, Jumpei Saito, Masato Fukae, Yu Egashira, Noritomo Izumi, Mariko Deguchi, Miyuki Kimura, Shunji Matsuki, Shin Irie, ICHIRO IEIRI, Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines., Scientific Reports, 6, 32299, 2016.08.
15. Makoto Kakara, Hiroko Nomura, Mai Ezaki, Masato Fukae, Takeshi Hirota, Sunao Matsubayashi, Masaaki Hirakawa, ICHIRO IEIRI, Population pharmacodynamic analysis of hemoglobin A1c-lowering effects by adding treatment of DPP-4 inhibitors (sitagliptin) in type 2 diabetes mellitus patients based on electronic medical records., Journal of Diabetes and its Complications, 30, 7, 1282-1286, 2016.09.
16. Tomoko Tokumoto, Takeshi Hirota, Keisuke Gotanda, Miyuki Kimura, Shin Irie, Masato Fukae, ICHIRO IEIRI, Effect of Curcumin on Sulfasalazine Pharmacokinetics in Healthy
Volunteers, Journal of Drug Metabolism & Toxicology, 80, 2, 2016.06.
17. Keisuke Gotanda, Tomoko Tokumoto, Takeshi Hirota, Masato Fukae, ICHIRO IEIRI, Sulfasalazine disposition in a subject with 376C>T (nonsense mutation) and 421C>A variants in the ABCG2 gene, Br J Clin Pharmacol, 80, 5, 1236-1237, 2015.11.
18. Takeshi Hirota, ICHIRO IEIRI, Drug-drug interactions that interfere with statin metabolism, Expert Opin Drug Metab Toxicol, 11, 9, 1435-1447, 2015.09.
19. Okada H, Kusaka T, Fuke N, Kunikata J, Kondo S, Iwase T, Nan W, Takeshi Hirota, Ieiri I, Itoh S, Neonatal Dubin-Johnson syndrome: Novel compound heterozygous mutation in the ABCC2 gene, Pediatr Int, 56, 5, e62-e64, 2014.10.
20. Yi, SoJeong, An, Hyungmi, Lee, Howard, Lee, Sangin, Ieiri, Ichiro, Lee, Youngjo, Cho, Joo-Youn, Takeshi Hirota, Fukae, Masato, Yoshida, Kenji, Nagatsuka, Shinichiro, et al.,, Korean, Japanese, and Chinese populations featured similar genes encoding drug-metabolizing enzymes and transporters: a DMET Plus microarray assessment, PHARMACOGENETICS AND GENOMICS, 10.1097/FPC.0000000000000075, 24, 10, 477-485, 2014.10.
21. Kenta Nishimura, Ryosuke Ide, Takeshi Hirota, Kana Kawazu, Shou Kodama, Hiroaki Takesue, ICHIRO IEIRI, Identification and Functional Characterization of Novel Nonsynonymous Variants in the Human Multidrug and Toxin Extrusion 2-K, Drug Metab Dispos, 10.1124/dmd.114.056887, 42, 9, 1432-1437, 2014.09.
22. Makoto Kakara, Hiroko Nomura, Masato Fukae, Keisuke Gotanda, Takeshi Hirota, Sunao Matsubayashi, Hideki Shimomura, Masaaki Hirakawa, ICHIRO IEIRI, Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records, Br J Clin Pharmacol, 2014.04.
23. Jumpei Saito, Takeshi Hirota, Shinji Furuta, Daisuke Kobayashi, Hiroshi Takane, ICHIRO IEIRI, Association between DNA methylation in the miR-328 5'-flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta, PLoS One, 8, 8, e72906, 2013.08.
24. Keisuke Gotanda†, Takeshi Hirota†, Nozomi Matsumoto, ICHIRO IEIRI, MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells († Equal contributors) , BMC Cancer, 13, 1, 369, 2013.08.
25. Yukie Ando, Hideaki Shimada, Nozomi Matsumoto, Takeshi Hirota, Motohiro Oribe, Eiji Otsuka, Kohji Ishii, Takuya Morimoto, Kyoichi Ohashi, ICHIRO IEIRI, Role of Methotrexate Polyglutamation and Reduced Folate Carrier 1 (RFC1) Gene Polymorphisms in Clinical Assessment Indexes, Drug Metabolism and Pharmacokinetics, 2013.04.
26. ICHIRO IEIRI, Shouhei Tsunemitsu, Kazuya Maeda, Yukie Ando, Noritomo Izumi, Miyuki Kimura, Naoe Yamane, Tsuyoshi Okuzono, Mariko Morishita, Naoki Kotani, Eri Kanda, Mariko Deguchi, Kyoko Matsuguma, Shunji Matsuki, Takeshi Hirota, Shin Irie, Hiroyuki Kusuhara, Yuichi Sugiyama, Mechanisms of pharmacokinetic enhancement between ritonavir and saquinavir; micro/small dosing tests using midazolam (CYP3A4), fexofenadine (p-glycoprotein), and pravastatin (OATP1B1) as probe drugs, Journal of Clinical Phamacology, 10.1002/jcph.62, 53, 6, 654-661, 2013.06.
27. Takeshi Hirota, Shunsuke Eguchi, ICHIRO IEIRI, Impact of Genetic Polymorphisms in CYP2C9 and CYP2C19 on the Pharmacokinetics of Clinically Used Drugs, DRUG METABOLISM AND PHARMACOKINETICS, 10.2133/dmpk.DMPK-12-RV-085, 28, 1, 28-37, 2013.02.
28. Ieiri I, Fukae M, Maeda K, Ando Y, Kimura M, Hirota T, Nakamura T, Iwasaki K, Matsuki S, Matsuguma K, Kanda E, Deguchi M, Irie S, Sugiyama Y., Pharmacogenomic/pharmacokinetic assessment of a four-probe cocktail for CYPs and OATPs following oral microdosing., Int J Clin Pharmacol Ther, in press, 2012.08.
29. Hirota T, Date Y, Nishibatake Y, Takane H, Fukuoka Y, Taniguchi Y, Burioka N, Shimizu E, Nakamura H, Otsubo K, Ieiri I., Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues., Lung Cancer, 77, 1, 16-23, 2012.07.
30. Ieiri I, Doi Y, Maeda K, Sasaki T, Kimura M, Hirota T, Chiyoda T, Miyagawa M, Irie S, Iwasaki K, Sugiyama Y., Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose., Journal of Clinical Pharmacology, 52, 7, 1078-89, 2012.07.
31. Saito J, Hirota T, Kikunaga N, Otsubo K, Ieiri I., Interindividual differences in placental expression of the SLC22A2 (OCT2) gene: Relationship to epigenetic variations in the 5'-upstream regulatory region., Journal of Pharmaceutical Sciences, 100, 9, 3875-83, 2011.09.
32. Ieiri I, Nishimura C, Maeda K, Sasaki T, Kimura M, Chiyoda T, Hirota T, Irie S, Shimizu H, Noguchi T, Yoshida K, Sugiyama Y., Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose., Pharmacogenet Genomics, 21, 8, 495-505, 2011.08.
33. Sasaki T, Hirota T, Ryokai Y, Kobayashi D, Kimura M, Irie S, Higuchi S, Ieiri I., Systematic screening of human ABCC3 polymorphisms and their effects on MRP3 expression and function., Drug Metabolism and Pharmacokinetics, 26, 4, 374-86, 2011.04.
34. Sasaki T, Takane H, Ogawa K, Isagawa S, Hirota T, Higuchi S, Horii T, Otsubo K, Ieiri I., Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect, thrombocytopenia, in Japanese patients., Antimicrob Agents Chemother, 55, 5, 1867-73, 2011.05.
35. Kanda D, Takagi H, Kawahara Y, Yata Y, Takakusagi T, Hatanaka T, Yoshinaga T, Iesaki K, Kashiwabara K, Higuchi T, Mori M, Hirota T, Higuchi S, Ieiri I., Novel large-scale deletion (whole exon 7) in the ABCC2 gene in a patient with the Dubin-Johnson syndrome., Drug Metab Pharmacokinet., 24, 5, 464-8, 2009.10.
36. Suwannakul S, Ieiri I, Kimura M, Kawabata K, Kusuhara H, Hirota T, Irie S, Sugiyama Y, Higuchi S., Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism., J Hum Genet, 53(10):899-904, 2008.07.
37. Hirota T, Takane H, Higuchi S, Ieiri I., Epigenetic regulation of genes encoding drug-metabolizing enzymes and transporters; DNA methylation and other mechanisms., Curr Drug Metab, 9(1):34-8, 2008.01.
38. Ieiri I, Takane H, Hirota T, Otsubo K, Higuchi S., Genetic polymorphisms of drug transporters: pharmacokinetic and pharmacodynamic consequences in pharmacotherapy., Expert Opin Drug Metab Toxicol., 2(5):651-74., 2006.10.
39. Kobayashi D, Ieiri I, Hirota T, Takane H, Maegawa S, Kigawa J, Suzuki H, Nanba E, Oshimura M, Terakawa N, Otsubo K, Mine K, Sugiyama Y., Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta., Drug Metabolism and Disposition, 10.1124/dmd.104.001628, 33, 1, 94-101, 33(1):94-101, 2005.01.
40. Hirota T, Ieiri I, Takane H, Maegawa S, Hosokawa M, Kobayashi K, Chiba K, Nanba E, Oshimura M, Sato T, Higuchi S, Otsubo K., Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic status., Human Molecular Genetics, 10.1093/hmg/ddh313, 13, 23, 2959-2969, 13(23):2959-69, 2004.12.
41. Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, Takane H, Irie S, Kusuhara H, Urasaki Y, Urae A, Higuchi S, Otsubo K, Sugiyama Y., Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics., Clinical Pharmacology & Therapeutics, 10.1016/S0009-9236(03)00060-2, 73, 6, 554-565, 73(6):554-65, 2003.06.
42. Takane H, Kobayashi D, Hirota T, Kigawa J, Terakawa N, Otsubo K, Ieiri I., Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene., Journal of Pharmacology And Experimental Therapeutics, 10.1124/jpet.104.069724, 311, 3, 1179-1187, 311(3):1179-87, 2004.12.
43. Hirota T, Ieiri I, Takane H, Sano H, Kawamoto K, Aono H, Yamasaki A, Takeuchi H, Masada M, Shimizu E, Higuchi S, Otsubo K., Sequence variability and candidate gene analysis in two cancer patients with complex clinical outcomes during morphine therapy., Drug Metabolism and Disposition, 31(5):677-80, 2003.05.

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