Bioequivalence evaluation of two sertraline tablet formulations in healthy male volunteers after a single dose administration.

ABSTRACT

SUBJECTS, MATERIAL AND METHODS: According to a randomized two-period crossover design, 12 Chinese male volunteers were treated with 2 sertraline tablet formulations, one was made in China as test tablet, the other was made in England as reference tablet. Each volunteer received each sertraline in a single dose of 150 mg. The 2 medications were carried out by a wash-out phase of 23 days. Blood samples were obtained just before dosing and at 10 time points until 96 hours after administration, and plasma sertraline concentrations were determined by a sensitive gas-chromagraphy electron-capture method with a lower limit of quantification of 0.625 ng/ml. The bioequivalence of 2 formulations was evaluated by the shortest 90% confidence interval method which corresponds to the two one-sided test method. RESULTS: The point estimate (90% confidence interval) of the mean ratio (test/reference) for AUC(0-96) was 97.19% (82.66% to 122.33%), for Cmax 96.27% (83.64% to 121.36%), and for t(l/2) 96.31% (85.43% to 119.57%). Regarding Tmax (test-reference), the 90% confidence interval ranged from -4 to +4 hours, but the difference between the Tmax values of 2 products is clinically of minor importance. CONCLUSION: Therefore, it can be concluded that 2 sertraline tablet formulations are bioequivalent. administration, sertraline is slowly absorbed with peak plasma concentrations at 6 - 8 h, and has a terminal elimination half-life of approximately 26 h, indicating once-daily dosing is available. Clinically, it can be taken either in the morning or in the evening, with or without food [Ronfeld et al. 1997b]. In addition, it also exhibits higher plasma protein binding up to 97% and extensive first-pass metabolism. By demethylation, sertraline is metabolized primarily to N-demethylsertraline, and then eliminated by hydroxylation arid conjugation [Tremaine et al. 1989]. This study aimed at assessing of bioequivalence of two sertraline formulations (produced in China and England, respectively) in healthy male volunteers after a single dose administration.