Bioequivalence of two oral ciprofloxacin formulations

Objective: To establish bioequivalence between two oral formulations of cip rofloxacin 500mg tablets (reference formulation: Cinaflox(R), BayerLaborato ries; test formulation: Cinaflox(R), SteinLaboratories). Design: A phase I crossover, randomised study with a 7-day washout period. Methods: A single dose of either drug was administered to 18 healthy male a nd female volunteers. Blood samples were drawn before each administration a nd on 14 occasions up to 24 hours after drug administration. Quantification of plasma concentrations was done by reverse-phase high performance liquid chromatography (HPLC). The area under the plasma concentration versus time curve for time zero to infinity (AUC(infinity)) was calculated by the trap ezoidal method, and maximum concentrations (C-max) and time to reach Cmax(t (max)) were obtained directly from the concentration versus time curves. C- max/AUC(infinity) was also calculated. After logarithmic transformation, an alysis of variance (ANOVA) was used for statistical analysis of AUC(infinit y), C-max and C-max/AUC(infinity), and t(max) was evaluated untransformed u sing the Mann-Whitney U-test. Classic confidence intervals (CI) and calcula tion of two one-sided t-tests (Schuirmann) were used as criteria for evalua tion of bioequivalence. Results and Conclusion: There were no gender, administration order or group biases. The mean values of the pharmacokinetic parameters obtained for the reference formulation were AUC(infinity) = 11.9457mg .h/L, C-max = 2.1622 mg/L, C-max/AUC(infinity) = 0.1837h(-1), t(max) = 1.55h. For the test formu lation, the mean values were AUC(infinity) = 11.1511mg .h/L, C-max = 1.9939 mg/L, C-max/AUC(infinity) = 0.1824h(-1), t(max) = 1.6388h. After compariso n of these four specific pharmacokinetic parameters for bioequivalence, it was concluded that, according to the recommendations of the 1992 European G uidelines (data transformed logarithmically and AUC(infinity) in the relati onship AUCt/AUC(infinity) greater than or equal to 80%), the test formulati on is bioequivalent in the extent (CI 85.0-104.0) and rate of absorption (C I 85.4-100.6) to the reference formulation. Since the difference between th e test and reference means for tmax was 0.07h, and the CI for C-max/AUC(inf inity) were 89.1 to 109.0, the two formulations are interchangeable. Both f ormulations were well tolerated; adverse effects reported were not clinical ly relevant.