关键词: 拉米夫定, 药代动力学, 高效液相色谱法, 生物等效性

Abstract: AIM: To develop a HPLC method for the determination of lamivudine in plasma and study the pharmacokinetics and relative bioavailability of domestic lamivudine tablet in Chinese healthy volunteers. METHODS: A single oral dose (0.3 g) of test tablet (domestic) or reference tablet (imported) was given to each volunteer according to an open randomized crossover study. The concentrations in plasma were determined by RP-HPLC method. The prepared sample was separated on the column of Kromasil C₁₈(250 mm×4.6 mmID,5 μm),with the mobile phase consisting of methanol-25 mmol/L potassium dihydrogen phosphate(containing of 1% triethylamine pH 3.3) (10∶90) at a flow rate of 1 mL/min. The eluted peaks were detected by UV detector at 280 nm. The pharmacokinetic parameters and relative bioavailability were calculated by DAS 2.1. RESULTS: The calibration curve was linear in the range of 25-7500 μg/L(r=0.9992). The relative recoveries of low, medium and high concentration were within 100.09%-103.36%. The intra-batch and inter-batch RSD were less than 2.2% and 7.8%, respectively. The main pharmacokinetic parameters of lamivudine were as follows: C_max were (2835±734) and (2868±726) μg/L;t_max were (1.15±0.60) and (1.05±0.78) h;t_1/2 were (2.68±0.32 ) and (2.58±0.41) h;AUC_{0-14 h} were (10994±1839) and (10593±1654) μg·L^-1·h;AUC_0-∞ were (11330±1908) and (10884±1734) μg·L^-1·h for test and reference preparations, respectively. The relative bioavailability of test tablet was(104.80±15.56)%. CONCLUSION: The assay method is simple, sensitive, accurate and good enough to be used in pharmacokinetic study of lamivudine. The results of statistical analysis show that two preparations in research are bioequivalent.

Key words: Lamivudine, Pharmacokinetics, HPLC, Bioequivalence