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在健康韩国受试者中,膳食盐对维拉帕米对映体与外排转运蛋白ABCB1基因多态性相关的处置没有影响。

Dietary salt does not influence the disposition of verapamil enantiomers in relation to efflux transporter ABCB1 genetic polymorphism in healthy Korean subjects.

作者信息

Pan W, Ryu J Y, Shon J H, Song I S, Liu K H, Sunwoo Y E, Kang W, Shin J G

机构信息

Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Jin-Gu, Busan, Korea.

出版信息

Xenobiotica. 2008 Apr;38(4):422-34. doi: 10.1080/00498250701832446.

Abstract

To evaluate the effects of dietary salt on the stereoselective disposition of verapamil enantiomers in relation to the transporter ABCB1 2677GG/3435CC and 2677TT/3435TT haplotypes, ten healthy subjects were asked to take diets of three different salt levels for 7 days in a randomized, three-way crossover manner. The plasma concentrations of verapamil and norverapamil enantiomers were determined after a single oral dose of 240 mg verapamil on the last day of each phase. Pharmacokinetic parameters were calculated by non-compartmental analysis techniques and compared among the three different dietary salt phases. Compared with the medium salt diet, the high and low salt diets had no significant effect on the disposition of verapamil enantiomers. Moreover, the ABCB1 haplotypes did not alter the impact of dietary salt, although ABCB1 2677TT/3435TT subjects had slightly, but not significantly, higher C(max) and area under the curve (AUC) and lower T(max) for the verapamil enantiomers than did 2677GG/3435CC subjects in each salt phase.

摘要

为评估饮食盐分对维拉帕米对映体立体选择性处置的影响,并探讨其与转运体ABCB1 2677GG/3435CC和2677TT/3435TT单倍型的关系,10名健康受试者按随机、三交叉方式,分别采用三种不同盐分水平的饮食,为期7天。在每个阶段的最后一天,受试者单次口服240 mg维拉帕米后,测定血浆中维拉帕米和去甲维拉帕米对映体的浓度。采用非房室分析技术计算药代动力学参数,并在三种不同饮食盐分阶段之间进行比较。与中等盐分饮食相比,高盐和低盐饮食对维拉帕米对映体的处置无显著影响。此外,ABCB1单倍型并未改变饮食盐分的影响,尽管在每个盐分阶段,携带ABCB1 2677TT/3435TT单倍型的受试者,其维拉帕米对映体的C(max)和曲线下面积(AUC)略高于携带2677GG/3435CC单倍型的受试者,而T(max)略低于后者,但差异均无统计学意义。

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