Evaluation of Bioequivalence of Two Formulations Containing 200 mg of Ketoconazole

Abstract

The bioequivalence of two oral formulations containing ketoconazole 200 mg was determined in 24 healthy Indian male volunteers. The study was designed as a single dose, two phase, two sequence cross-over study with a wash out period of one week. The content of ketoconazole in plasma was determined by a validated HPLC method using BDS Hypersil C18, (250 × 4.6 mm 5 μ particle size) column. The mobile phase consisted of 0.1 M disodium hydrogen phosphate buffer (pH adjusted to 6.0 with glacial acetic acid) and acetonitrile in the ratio of 60:40 v/v and eluted at a flow rate of 1 mL/min. The eluent was monitored using UV detection at 240 nm. The preparations were compared using the parameters area under the plasma concentration-time curve (AUC0_-∞), peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the logarithmic transformed AUC0_-∞ and Cmax values of the two preparations. The 90 % confidence interval for the ratio of the logarithmic transformed AUC0_-∞ and Cmax were within the bioequivalence limit of 0.80-1.25. Moreover, the elimination rate constant (Kel) and elimination half life (t_½) values obtained with the two preparations were comparable and not significantly different statistically.