RELATIVE BIOAVAILABILITY OF THE ANTIARRHY THMIC AGENT TIRACIZINE AND 3 OF ITS METABOLITES

Relative bioavailability of a 100 mg tablet formulation of the antiarr hythmic agent tiracizine (CAS 78816-67-8) compared to a 50 mg formulat ion was assessed in a simple cross over study after single administrat ion of a 100 mg dose to 12 healthy volunteers. Tiracizine and three of its metabolites (M1, M2 and M3) were measured in serum and urine by h igh pressure liquid chromatography. AUC (means after administration of the test preparation and 95% nonparametric confidence interval the ra tio test preparation/reference preparation) were 391.5 ng . h/ml 0.87- 1.11 for tiracizine, 5184.5 ng . h/ml and 0.94-1.26 for M1, and 1319.9 ng . h/ml and 0.88-1.16 for M2. Mean maximum serum concentrations aft er the test preparation and corresponding 95% confidence interval were 111.2 ng/ml and 0.86-1.20 for tiracizine, 301.2 ng/ml and 0.98-1.22 f or M1, 54.6 ng/ml and 0.86-1.17 for M2, and 35.2 ng/ml and 0.82-1.17 f or M3. t(max) did not differ after the two preparations for tiracizine , M2 and M3, but was significant lower for M1 after administration of the test preparation (2.2 +/- 0.7 vs 3.0 +/- 1.2 h). Total urinary rec overy (sum of parent compound and metabolite, recovery) up to 32 h aft er intake of the test preparation was 31.2% of the administered dose. The corresponding 95% confidence interval was 0.84-1.08. Statistical e valuation of all parameters revealed bioequivalence between the two pr eparations if a single doseof 100 mg is administered.