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

Archives of Pharmacal Research 2020년 43권 11호 p.1187 ~ 1196
신효빈, 정의현, 강푸름, 임창우, 오경열, 조창근, 이윤정, 최창익, 장춘곤, 이석용, 배정우,
소속 상세정보
신효빈 ( Shin Hyo-Bin ) - Sungkyunkwan University School of Pharmacy
정의현 ( Jung Eui-Hyun ) - Sungkyunkwan University School of Pharmacy
강푸름 ( Kang Pu-Reum ) - Sungkyunkwan University School of Pharmacy
임창우 ( Lim Chang-Woo ) - Sungkyunkwan University School of Pharmacy
오경열 ( Oh Kyung-Yul ) - Sungkyunkwan University School of Pharmacy
조창근 ( Cho Chang-Keun ) - Sungkyunkwan University School of Pharmacy
이윤정 ( Lee Yun-Jeong ) - Dankook University College of Pharmacy
최창익 ( Choi Chang-Ik ) - Dongguk University College of Pharmacy
장춘곤 ( Jang Choon-Gon ) - Sungkyunkwan University School of Pharmacy
이석용 ( Lee Seok-Yong ) - Sungkyunkwan University School of Pharmacy
배정우 ( Bae Jung-Woo ) - Keimyung University College of Pharmacy

Abstract


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 Cmax of losartan and losartan plus E-3174 (Lo?+?E) among the three diplotype groups (both P?T/c.3435C>T diplotypes of ABCB1 may significantly increase the early-phase absorption of losartan, but not the total absorption.

키워드

Losartan; ABCB1; MDR1; Diplotype; Pharmacogenomics; Pharmacokinetics

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