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首页> 外文期刊>Xenobiotica: the fate of foreign compounds in biological systems >Effects of OCT2 c.602C > T genetic variant on the pharmacokinetics of lamivudine
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Effects of OCT2 c.602C > T genetic variant on the pharmacokinetics of lamivudine

机译：OCT2 c.602C> T基因变异对拉米夫定药代动力学的影响

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1. The renal excretion of organic cation drugs, including lamivudine, is mostly mediated by OCT2 in vitro. To date, three putatively relevant single nucleotide polymorphisms (SNPs), including c.596C > T (p.Thr199Ile), c.602C > T (p.Thr201Met), and c.808G > T (p.Ala270Ser) have been observed in Asians. The effects of the SLC22A2 c.602C > T genetic variant on the pharmacokinetics of lamivudine were studied with healthy Korean subjects. 2. Nineteen healthy subjects carrying either the SLC22A2 c.602CC (n = 12) or c.602CT (n = 7) genotype volunteered for this study. A single 100 mg dose of lamivudine was orally administered to each subject. Blood samples were collected for up to 24 h and the plasma concentrations of lamivudine were measured using liquid chromatography-tandem mass spectrometry. 3. The mean plasma concentration-time profiles of lamivudine in the c.602CC and c.602CT genotype groups were similar. There was no significant difference in the overall pharmacokinetic parameters of lamivudine between the c.602CC and c.602CT genotype groups. Differences in renal clearance and tubular secretion clearance were also not statistically significant between the two genotype groups. 4. The SLC22A2 c.602C > T genotype did not affect the pharmacokinetics of lamivudine in humans in vivo. Dose adjustment of lamivudine is not required between individuals with c.602CC and c.602CT genotypes.
机译：1.包括拉米夫定在内的有机阳离子药物的肾脏排泄主要由体外OCT2介导。迄今为止，已经观察到三个推定相关的单核苷酸多态性（SNP），包括c.596C> T（p.Thr199Ile），c.602C> T（p.Thr201Met）和c.808G> T（p.Ala270Ser）。在亚洲人中在韩国健康受试者中研究了SLC22A2 c.602C> T基因变异对拉米夫定药代动力学的影响。 2.自愿携带SLC22A2 c.602CC（n = 12）或c.602CT（n = 7）基因型的19位健康受试者参加了本研究。向每个受试者口服单次100 mg剂量的拉米夫定。收集血样长达24小时，并使用液相色谱-串联质谱法测量拉米夫定的血浆浓度。 3.拉米夫定在c.602CC和c.602CT基因型组中的平均血浆浓度-时间曲线相似。拉米夫定的总体药代动力学参数在c.602CC和c.602CT基因型组之间没有显着差异。在两个基因型组之间，肾清除率和肾小管分泌物清除率的差异也无统计学意义。 4. SLC22A2 c.602C> T基因型不影响拉米夫定在人体中的体内药代动力学。具有c.602CC和c.602CT基因型的个体之间不需要拉米夫定的剂量调整。

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