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Abstract
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.