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

ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan. Arch Pharm Res. 2020 Nov 29;: Authors: Shin HB, Jung EH, Kang P, Lim CW, Oh KY, Cho CK, Lee YJ, Choi CI, Jang CG, Lee SY, Bae JW 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 < 0.01). However, the power of the performed test is less than the desired power (0.800). The tmax of losartan and E-3174 in three diplotype groups were also significantly different (both P < 0.01). The AUC values of Lo + E were significantly different am...
Source: Archives of Pharmacal Research - Category: Drugs & Pharmacology Authors: Tags: Arch Pharm Res Source Type: research