RELATIVE BIOAVAILABILITY OF 4 CLOMIPRAMINE HYDROCHLORIDE TABLET PRODUCTS

The relative bioavailability of clomipramine was determined in two sin gle-blind, single-dose, randomized, crossover studies. In the first st udy, the relative bioavailability of the test product, 2 x 25 mg clomi pramine hydrochloride tablets (Noristan Ltd.), with respect to the ref erence product, Anafranil(R) 2 x 25 mg tablets (clomipramine HCl; Ciba -Geigy (Pty) Ltd.) was determined. In the second study, the relative b ioavailability of the test product, 5 x 10 mg clomipramine hydrochlori de tablets (Noristan Ltd.), with respect to the reference product, Ana franil(R) 5 x 10 mg tablets (clomipramine HCl; Ciba-Geigy (Pty) Ltd.), was determined. The geometric mean values for the variable C-max were 31.3 ng mL(-1) for the reference and 31.6 ng mL(-1) for the test prod uct in study 1. The geometric mean values for the variable AUC were 73 6 ng h mL(-1) and 753 ng h mL(-1) for the reference and test, respecti vely. In study 2, the geometric mean C,, values were 25.8 ng mL(-1) an d 23.9 ng mL(-1) for the reference and test respectively; the geometri c mean AUC values were 569 ng h mL(-1) and 547 ng h mL(-1). The 90% co nfidence intervals for the 'test/reference' mean ratios of the plasma clomipramine pharmacokinetic variables C-max and AUC((0-infinity)) (as measures of the rate and extent of absorption of clomipramine, respec tively) fail within the conventional bioequivalence range of 80-125% f or both studies. The test products (clomipramine HCl) are therefore bi oequivalent to the reference products (Anafranil(R)) with respect to t he rate and the extent of absorption of clomipramine in both 10 mg and 25 mg strengths.