BIOEQUIVALENCE AND PHARMACOKINETICS OF CHLORPHENERAMINE IN HEALTHY-HUMAN VOLUNTEERS

This study was carried out to evaluate the bioavailability of a new re gular release tablet formulation of chlorphenamine (CPA) (Histop) rela tive to a reference formula (Piriton) using 13 human healthy volunteer s. Each one received the two formulations as two 4 mg tablets in a two -way double-blind, crossover study. The concentration of CPA was measu red with a sensitive high performance liquid chromatography (HPLC). Th e geometric mean for the area under the curve up to the last concentra tion (AUG (0-t)), to infinity (AUC(0-oo)) and the maximum concentratio n (Cp max) were 316.5, 315 + 439.8, 431.2 (ngh/ml) and 22, 20.5 (ug/ml ) for the test (T) and reference (R) formulations, respectively. The p arametric 90% confidence intervals of T/R ratio of the above parameter s were within the bioequivalence acceptable range of 80 - 125%. The me an time to the maximum concentration T-max (h) were 2.5 and 2.03 for t he two formulations respectively and the parametric 90% confidence int ervals of the T-max difference (T-R) were in the range of -0.26 - 1.14 h, with point estimate of 0.44 h. The two formulations were found to be bioequivalent by the Schuirmann two one-sided t-test. Based on the pharmacokinetic results obtained frequent (ie., Q 4 - 6 h) CPA daily d osing may not be required particularly for the adults because of its l ong elimination half-life.