No association between OCT2 C602T genetic variant and the pharmacokinetics of lamivudine

Purpose: Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for the treatment of human immunodeficiency virus (HIV) and chronic hepatitis B. It is reported that the renal excretion of lamivudine is mostly mediated by OCT2, an influx transporter encoded by SLC22A2 gene. We investigated the effects of OCT2 C602T variant on the pharmacokinetics of lamivudine.

Methods:  Nineteen healthy volunteers were selected and they were divided into two groups according to OCT2 C602T genotype, c.602CC (CC type, n=12) and c.602CT (CT type, n=7). Each subject received a single oral dose of 100 mg lamivudine. Blood samples were collected up to 24 hr after drug intake, and the concentrations of lamivudine in plasma samples were determined by using LC-MS/MS system.

Results: No significant differences in the C_max and AUC values of lamivudine were observed between CC type and CT type. C_max of lamivudine in CC type and CT type was 1150.0 ± 191.4 ng/mL and 1255.6 ± 249.8 ng/mL, respectively. AUC_inf of lamivudine in each genotype group was 4429.4 ± 427.5 ng∙hr/mL and 4297.4 ± 1047.9 ng∙hr/mL, respectively. Oral clearance (CL/F) and elimination half-life (t_1/2) of lamivudine were not also statistically significant between two genotype groups.

Conclusion:  OCT2 C602T genetic variant did not affect the pharmacokinetics of lamivudine. Further study with the subjects homozygous for the T-allele will be needed.