Abstract

The present work aimed to compare the relative bioavailability of Zolapin with 100 mg tablet Leponex as a reference formulation, through a simple, robust and low-cost bioequivalence assays method. The study design was multiple-dose, randomized, crossover with patients in steady-state, and was performed with 24 schizophrenic male patients. Subjects received 100 mg twice a day of either Leponex or Zolapin for 10 days. At day 10 days of each study phase, blood samples were collected at different times during 12 h after drug administration and the clozapine concentration was determined by high performance liquid chromatography (HPLC). The individual peak plasma concentrations (Cmax) and the area under the concentration-time curve (AUC0-12h) ratios were calculated. The evaluated pharmacokinetic parameters were quite similar for both formulations. The 90% confidence interval for mean ratio of lnCmax (0.9677 to 0.9937) and lnAUC0-12h (0.9811 to 1.0029) were within accepted international guidelines. The results demonstrate that this methodological approach was able to identify Zolapin as bioequivalent to Leponex when orally administered, both in terms of the rate and extent of absorption, and therefore, suitable as a potential low-cost alternative to branded antipsychotic drugs.

Key words: Clozapine, bioavailability, pharmacokinetics, schizophrenia.