2013 Fiscal Year Final Research Report
Regional Difference in the Effect of Influx/Efflux Transporters and Metabolic Enzymes on Intestinal Drug Absorption
| Project/Area Number |
23590175
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
IKUMI Tamai 金沢大学, 薬学系, 教授 (20155237)
TAKEO Nakanishi 金沢大学, 薬学系, 准教授 (30541742)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 薬学 / 薬物動態学 / 経口吸収 / 徐放性製剤 / トランスポーター / 代謝酵素 / 薬物間相互作用 / 生体分子 |
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| Research Abstract |
In the present study, we aimed to clarify the site-specific contribution of transporters and metabolic enzymes to the intestinal drug absorption. The rat in situ studies with talinolol and colchicine demonstrated site-specific drug absorption presumably due to differential expression and function of OATP and P-gp. Further analysis revealed presence of multiple binding sites on OATP2B1 with different affinity for drugs. Meanwhile, microsomal studies demonstrated that CYP3A5 genotype and expression level have a significant impact on inhibitory potency for CYP3A-catalyzed drug metabolism, but that the magnitude of its effect is inhibitor-substrate pair specific. The results of the study focusing on CYP2C19 show that, although metabolites contribute to in vivo DDIs, their relative abundance in circulation does not predict their contribution to in vivo DDI risk. These findings revealed involvement of influx/efflux transporters and metabolic enzymes in the intestinal drug absorption process.
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[Journal Article] MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid2013
Author(s)
Kugai M, Uchiyama K, Tsuji T, Yoriki H, Fukui A, Qin Y, Higashimura Y, Mizushima K, Yoshida N, Katada K, Kamada K, Handa O, Takagi T, Konishi H, Yagi N, Yoshikawa T, Shirasaka Y, Tamai I, Naito Y, and Itoh Y
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Journal Title
Cell Physiol Biochem
Volume: 32(4)
Pages: 942-950
Peer Reviewed
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[Journal Article] Involvement of Functional Groups on the Surface of Carboxyl Group-Terminated Polyamidoamine Dendrimers Bearing Arbutin in Inhibition of Na(+)/Glucose Cotransporter 1 (SGLT1)-Mediated d-Glucose Uptake2012
Author(s)
Sakuma S, Kanamitsu S, Teraoka Y, Masaoka Y, Kataoka M, Yamashita S, Shirasaka Y, Tamai I, Muraoka M, Nakatsuji Y, Kida T, and Akashi M
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Journal Title
Mol Pharm
Volume: 9(4)
Pages: 922-929
Peer Reviewed
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[Presentation] Interindividual Variability of CYP2C19-Catalyzed Drug Metabolism Due to Differences in the Diplotypes2013
Author(s)
Yoshiyuki Shirasaka, Amarjit S. Chaudhry, Timothy Wong, Justina C. Calamia, Nina Isoherranen, Allan E. Rettie, Erin G. Schuetz, and Kenneth E. Thummel
Organizer
10th International ISSX Meeting
Place of Presentation
The Westin Harbour Castle, Toronto, Ontario, Canada
Year and Date
20130930-1003
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[Presentation] Impact of CYP3A5 Expression on the Inhibition of CYP3A-Catalyzed Drug Metabolism : Considerations for Modeling CYP3A-Mediated Drug-Drug Interactions2012
Author(s)
Yoshiyuki Shirasaka, Chi-Chi Peng, Shu-Ying Chang, Mary F. Grubb, Stephen R. Johnson, A. David Rodrigues, Kenneth E. Thummel, and Nina Isoherranen
Organizer
18th North American Regional ISSX Meeting
Place of Presentation
Hilton Anatole Dallas Hotel, Dallas, Texas, USA
Year and Date
2012-10-15
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