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KMID : 0043320200430111187
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Archives of Pharmacal Research
2020 Volume.43 No. 11 p.1187 ~ p.1196
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ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan
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Shin Hyo-Bin
Jung Eui-Hyun
Kang Pu-Reum
Lim Chang-Woo
Oh Kyung-Yul
Cho Chang-Keun
Lee Yun-Jeong
Choi Chang-Ik
Jang Choon-Gon
Lee Seok-Yong
Bae Jung-Woo
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Abstract
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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.
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KEYWORD
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Losartan, ABCB1, MDR1, Diplotype, Pharmacogenomics, Pharmacokinetics
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