| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Outline of Final Research Achievements |
Endogenous biomarkers are considered important in drug development to advance transporter-mediated drug-drug interaction (DDI) risk assessment. Drug interaction studies with OATP1B inhibitors and OAT inhibitors that caused transporter-mediated drug interactions identified metabolites and their pharmacokinetic parameters associated with transporter activities. Based on a genome-wide association analysis of serum metabolite profiles, a metabolite was selected as candidate OCT2 biomarker which was supported by non-clinical studies on renal organic cation transporters. We obtained information on transcriptional regulation as a underlying mechanism by which polymorphisms affect OCT2 expression. In the samples administered with irinotecan, the biomarkers were quantified which help understanding the relationship with the transporter activities and interindividual difference in the plasma concentrations of irinotecan and its active metabolites.
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