Developments in estimation of the functional changes of transporters and drug metabolizing enzymes during renal failure

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18934
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: Masuo Yusuke 金沢大学, 薬学系, 助教 (90708140)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: トランスポーター / 慢性腎障害 / 尿毒素 / メタボロミクス

Outline of Final Research Achievements

Several uremic tocxins have been proposed to inhibit hepatic uptake transporters. The purpose of this study is to find possible inhibition of OATP1B1 by newly identified uremic toxins, 6-OH indole. 6-OH indole inhibited OATP1B1-mediated uptake of [3H]estrone sulfate in HEK293/OATP1B1 cells. Plasma concentration of 6-OH indole was higher in patients with severe renal failure than that in patients without renal failure. The inhibition pattern of OATP1B1 by 6-OH indole was long-lasting, since its inhibition was maintained after 6-OH indole was washed out. Also, 6-OH indole inhibited uptake of estrone sulfate in primary cultured hepatocytes without changing mRNA expression of OATP1B1. These results suggest that increase of 6-OH indole in plasma during CKD could at least partially explain the delayed elimination of OATP1B1 substrate drugs.

Free Research Field

薬物治療学