ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan

Losartan has been shown to be a substrate of the drug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and function of P-glycoprotein (P-gp). We investigated the effects of ABCB1 diplotype on the pharm...

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Published in:Archives of pharmacal research 2020, 43(11), , pp.1187-1196
Main Authors: Shin, Hyo-Bin, Jung, Eui Hyun, Kang, Pureum, Lim, Chang Woo, Oh, Kyung-Yul, Cho, Chang-Keun, Lee, Yun Jeong, Choi, Chang-Ik, Jang, Choon-Gon, Lee, Seok-Yong, Bae, Jung-Woo
Format: Article
Language:English
Subjects:
Medicine
Pharmacology/Toxicology
Pharmacy
Research Article
약학
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Summary:Losartan has been shown to be a substrate of the drug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and function of P-glycoprotein (P-gp). We investigated the effects of ABCB1 diplotype on the pharmacokinetics of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T; carriers of GG/CC (n = 13), GT/CT (n = 12) and TT/TT (n = 13) diplotype] were recruited and administered a single 50 mg oral dose of losartan potassium. Losartan and its active metabolite E-3174 samples in plasma and urine were collected up to 10 and 8 h after drug administration, respectively, and the concentrations of both samples were determined by HPLC method. Significant differences were observed in C max of losartan and losartan plus E-3174 (Lo + E) among the three diplotype groups (both P  
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-020-01294-3