Bioavailability of ketoconazole tablets commercially available in Thailand

Abstract

Nine brands of 200 mg ketoconazole tablets commercially available in Thailand were evaluated. In vitro studies revealed that each brand met the United State Pharmacopoeia XXII specification for drug content, content uniformity and disintegration times. However, major differences were observed among brands in their rates of dissolution in both simulated gastric fluid and simulated intestinal fluid. Only five brands of 200 mg ketoconazole tablets were selected for in vivo evaluation. One was an innovator’s product (A) which was assigned to be as a reference standard and others were those having different dissolution rates in simulated gastric fluid (B, C, D and E). The study was conducted using a single dose (200 mg) cross over desing in 12 healthy volunteers. Blood samples were collected at appropriate times and were assayed using HPLC. Data analysis computed by the computer programs CSTRIP&SAP demonstrated that there were no statistically significant differences of the relevant pharmacokinetic parameters (Cmax’ tmax and AUC) among the five brands and between each other indicating that all brands tested were completely bioequivalent. The relative bioavailabilities of brands B, C, D and E with respect to brand A were 104.00, 99.47, 108.69, and 101.76% ,respectively. No statistically significant correlation were observed between the in vivo and the in vitro parameters studied. The pharmacokinetics of 200 mg ketoconazole tablets were well described by one compartment open model with first order absorption and elimination and no lag time. The drug was rapidly absorbed with the absorptive rate constant ranged from 1.12 to 1.64 hr-1, and the biologic half-life were between 2.28 to 2.80 hr.