Pharmacokinetics and bioequivalence studies of warfarin sodium 5 milligrams tablet in healty thai subjects

• Main Authors: Sornsuvit,C., Niamhun,N., Luengpiansamut,N., Sangsrijan,S., Niwatananum,W., Kaewvichit,S., Hongwiset,D., Nuntachit,N., Yotsawimonwat,S.
• Format: Article
• Published: IJPPS 2015
• Subjects: Pharmaceutical Science; Pharmacology
• Online Access: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84924360041&origin=inward; http://cmuir.cmu.ac.th/handle/6653943832/38559
• Institution: Chiang Mai University

© 2015, International Journal of Pharmacy and Pharmaceutical Science. All rights reserved. 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 Cmax, Tmax, t1/2 and AUC0-72h. 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 Cmax values were 759.63 and 778.20 ng/ml and the mean AUC0-72h 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 Cmax, and AUC0-72h, respectively. The 90% confidence intervals of the ratios of Cmax and AUC0-72h 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.