Bioequivalence of two rimantadine tablet formulations in healthy male volunteers after single dose administration

Aim: The bioequivalence of two rimantadine tablet formulations was determin ed. Methods: The study was designed as a randomized, two-period, two-sequen ce, crossover study. Twenty-four healthy male volunteers received a single 100 mg; dose of rimantadine hydrochloride as test (Rimantadin Lachema 100 t bl. obd., produced by Lachema, a.s., Brno, Czech Republic) and reference fo rmulations (Flumadine 100 tbl. obd., produced by Forest Pharmaceuticals, St . Louis, USA). The two administrations were separated by 14 days and were p erformed in the fasting state. Blood samples were obtained at 15 time point s during the interval 0 - 120 h after administration. Rimantadine plasma co ncentrations were determined by gas chromatography with electron-capture de tection. Results: The geometric mean concentration-time profiles of rimanta dine after administration of the two formulations were superimposable. The following pharmacokinetic parameters refer to the geometric mean [exp(mean SD)] values for the test and reference formulations, respectively: C-max (n g/ml) 70.5 (60.0 - 82.7) vs. 70.0 (59.9 to 81.7), AUC(0-infinity) (ng x h/m l) 2872 (2224 to 3707) vs. 2849 (2195 - 3699), AUC(0-120h) 2744 (2184 - 344 8) vs. 2712 (2138 - 3441), t(1/2) (it) 25.8 (20.1 - 33.0) vs. 25.7 (20.6 to 32.1). Median (range) t(max) (h) values were 4.5 (2.0 - 8.0) and 6.0 (10 - 8.0). parametric 90% confidence intervals for the expected mean percentage ratios (test/reference) of the pharmacokinetic variables were within the r ange of 97% to 105%. The median (91.1% confidence interval) difference in t (max) was -0.3 h (-2.0 -0.5). The point and interval estimates were identic al when truncated AUCs (0-96 h, 0-72 h, 0-48 h and 0-24 h) were used in cal culations. Conclusion: The two rimantadine formulations were equivalent in both the rate and extent of bioavailability and they were also well tolerat ed. This study confirms the findings of other studies showing that for imme diate release formulations of drugs with long half-lives shortening the dur ation over which blood samples are collected improves the economics, is mor e ethical and does not impair the quality of data.