Relative bioavailability of imipramine (tofranil) coated tablets in healthy volunteers

Objectives: Imipramine is a tricyclic antidepressant drug with a considerab le hepatic first-pass metabolism resulting in highly variable pharmacokinet ic characteristics and desipramine as active major metabolite. This study d escribes the bioavailability of 3 formulations of imipramine. Methods: In a randomized, three-period crossover study, 18 healthy male Caucasian subjec ts received single oral doses of Tofranil 25, Tofranil mite (10 mg) and an aqueous solution containing 25 mg imipramine-HCl. Serum concentrations of i mipramine-HCl and its main metabolite desipramine were measured. The pharma cokinetic characteristics, C-max, AUC, t(1/2) and t(max) were determined an d the relative bioavailability of the two coated tablet formulations was ca lculated with the aqueous solution as reference. Safety and tolerability we re assessed using vital signs, ECG, clinical laboratory and adverse event r ecording. Results: The relative bioavailabilities of Tofranil 25 and Tofran il mite were 97% and 81%, respectively. The study medication was well toler ated. Conclusions: A sufficiently high extent of absorption was found for t he test formulations ensuring therapeutic efficacy.