Evaluation of Average Bioequivalence of Two Oral Formulations of Amiodarone Hydrochloride after Single Administration to Healthy Volunteers Ivanka Atanasova 1 and Dimiter Terziivanov 2 1 Laboratory of Clinical Pharmacology and Pharmacokinetics, Chemical Pharmaceutical Research Institute, Sofia, Bulgaria 2 Clinic for Therapeutics and Clinical Pharmacology, University Hospital, ‘St Ivan Rilsky’, Sofia, Bulgaria Abstract Objective: To assess the average bioequivalence of two oral forms of amiodarone hydrochloride, amiodarone (Balkanpharma Co., Bulgaria) [test] and Cordarone ® (Sanofi, France) [reference] in healthy volunteers. Design: Single-dose, balanced, two-period, two-treatment, crossover study. Participants: 24 healthy Caucasian volunteers (12 men and 12 women) took part in the study. Methods: Participants received single doses of amiodarone 400mg (2 × 200mg tablets) with a washout period of 30 days between treatments. Plasma samples were taken at regular time intervals according to the study protocol for measuring plasma amiodarone and desethylamiodarone concentrations. The primary and secondary parameters area under the plasma concentration-time curve from zero to infinity (AUC0-∞), maximum plasma concentration (Cmax ), time to reach maximum concentration (tmax ) and mean residence time (MRT) were estimated. The point estimates (geometric means) of the test/reference ratio and the 90% confidence intervals (CIs) for the ratios of expected medians, assuming a multi- plicative model, estimated by parametric and nonparametric analyses, were tested for inclusion in the defined bioequivalence range for the primary parameters. Results: The point estimates and the 90% CIs of the ratios of AUC0- ∞ and Cmax after parametric analysis were 0.96 (0.87 to 1.06) and 1.02 (0.86 to 1.21), respec- tively. The two products were considered to be bioequivalent in their extent and rate of absorption. However, analysis of variance (ANOVA) revealed significant interindividual and between-period variability in the primary parameters AUC0- ∞ and Cmax . Conclusions: The average extent and rate of absorption of the test and reference products containing amiodarone hydrochloride 200mg per tablet were not signif- icantly different. However, there was significant variability among individuals and between periods in AUC0-∞ and Cmax . Therefore, prescribing the test product is appropriate, but switching between products is not recommended. CLINICAL PHARMACOKINETICS Clin Drug Invest 2001; 21 (6): 423-428 1173-2563/01/0006-0423/$22.00/0 © Adis International Limited. All rights reserved.