Abstract
The comparative bioavailability of a new tablet formulation of fluphenazine dihydrochloride (5 mg) and a reference product (fluphenazine dihydrochloride, Prolixin, 5 mg) was assessed in drug-free psychiatric patients. Twenty-six patients were initially entered in the study, of whom 22 completed the protocol. Each patient received the test (T) and the reference formulation (R) in a balanced two-way crossover design. Plasma concentrations of fluphenazine were monitored over a period of 48 h after drug administration using a sensitive HPLC method. One patient did not show any measurable plasma concentration for one formulation at any sampling time and, therefore, bioavailability was assessed in the remaining 21 patients. All pharmacokinetic parameters showed wide intersubject variation. The maximum plasma concentration (Cmax), time to Cmax, and area under the curve up to the last measurable concentration (AUClasto), infinity (AUC∞o), or truncated areas (such as AUC16o, AUC24o) were compared by analyses of variance and found not to be significantly different in each case across the formulations. Except for AUC24o, AUC32o, and AUC48o, ANOVA of all other parameters showed a high power (>80%) to detect a 20% difference in the mean value of each bioequivalence parameter between T and R. The two formulations were found to be bioequivalent in that confidence intervals of the mean values of AUC∞o, AUClasto, truncated AUCs, or Cmax for T : R ratios were, in each case, well within the acceptable range of 100 ± 20%.
Published Version
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