Cha Yu Jung, Ghim Jong Lyul
Department of Clinical Pharmacology and Toxicology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
J Korean Med Sci. 2017 Sep;32(9):1542-1547. doi: 10.3346/jkms.2017.32.9.1542.
Oseltamivir is a substrate of P-glycoprotein, an efflux drug transporter encoded by ABCB1. The objective of this study was to assess the role of ABCB1 (c.1236C>T, c.2677G>T/A, and c.3435C>T) polymorphisms in the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate in humans. Nineteen healthy male subjects were enrolled, and their ABCB1 polymorphisms were evaluated. After the oral administration of 75 mg oseltamivir, the plasma concentrations of oseltamivir and oseltamivir carboxylate were measured. Pharmacokinetic analysis was carried out. Systemic exposure to oseltamivir and oseltamivir carboxylate was higher in the mutant group than in the wild-type and heterozygous groups. We suggest that ABCB1 polymorphisms affect the pharmacokinetics of oseltamivir in humans. Further studies in a large population are necessary to validate the results of this preliminary study (Clinical Trial Registration Information [CRIS] registry: http://cris.nih.go.kr, No. KCT0001903).
奥司他韦是P-糖蛋白的底物，P-糖蛋白是一种由ABCB1编码的外排药物转运蛋白。本研究的目的是评估ABCB1基因多态性（c.1236C>T、c.2677G>T/A和c.3435C>T）对奥司他韦及其活性代谢产物奥司他韦羧酸盐在人体药代动力学中的作用。招募了19名健康男性受试者，并对他们的ABCB1基因多态性进行了评估。口服75 mg奥司他韦后，测量了奥司他韦和奥司他韦羧酸盐的血浆浓度，并进行了药代动力学分析。突变组中奥司他韦和奥司他韦羧酸盐的全身暴露量高于野生型和杂合子组。我们认为ABCB1基因多态性会影响奥司他韦在人体中的药代动力学。需要在大量人群中进行进一步研究以验证本初步研究的结果（临床试验注册信息[CRIS]登记号：http://cris.nih.go.kr，编号KCT0001903）。
