PHARMACOKINETICS AND BIOEQUIVALENCE STUDIES OF WARFARIN SODIUM 5 MILLIGRAMS TABLET IN HEALTY THAI SUBJECTS

摘要

Objective: The present study aimed to evaluate the bioequivalence between the generic warfarin sodium tablet and a reference product when gave as equal labeled doses in healthy Thai subjects under fasting condition. Methods: A randomized, open-label, single dose, two treatments, two periods, two sequences, crossover design between 5 mg of warfarin administration under fasting condition was conducted in 22 male and female healthy Thai subjects. Each subject was assigned randomly to receive a single oral dose of the test formulation or the reference formulation of 5 mg warfarin tablets. Study periods were separated by a 14-day washout period. Blood samples were collected at 0.0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 8.0, 12.0, 24.0, 36.0, 48.0 and 72.0 h after drug administration. A simple, sensitive and specific HPLC method was used for quantification of warfarin in plasma. Pharmacokinetic parameters were analyzed including C max , T max , t1/2 and AUC 0-72h . Results: Twenty subjects, selected randomly from healthy adult Thai subjects were enrolled, age of 22.5 + 3.1 years, weight, 59 + 6 kg. Twenty-one subjects completed both periods of the study. The mean C max values were 759.63 and 778.20 ng/ml and the mean AUC 0-72h were 20010.89 and 20418.55 ng. h./ml for test and reference formulations, respectively. The mean ratios for log-transformed data were 0.9955 and 0.9971 for C max , and AUC 0-72h , respectively. The 90% confidence intervals of the ratios of C max and AUC 0-72h between test and reference tablets were 88.23% – 105.70% and 94.40% – 99.61%. Conclusion: It can be concluded that test and reference warfarin 5 mg products were bioequivalent in terms of rate and extent of absorption. Keywords: Pharmacokinetic, Bioequivalence, Warfarin, HPLC, Validation, Human plasma.