Bioequivalence Study of Two Formulations That Contain Isotretinoin 20 mg Capsules in Healthy Colombian Volunteers

Abstract

This is a pharmacokinetic test of two formulations that contain 20 mg of Isotretinoin, with the aim to compare the bioavailability between the Test Product (Isoface® from Procaps Laboratory SA, Colombia) and the Reference Product (Roaccutane® from Catalent Laboratory Germany, Eberbach GMBH, Germany), to declare the bioequivalence between both formulations. An open, crossed study was developed, randomized, of two periods and two sequences, with 40 mg single dose of isotretinoin, on fasting conditions, on 24 healthy male Colombian volunteers; the washout was 14 days in between each period. To present the results, curves of the plasma concentration ratio vs. Time until hour 72 were performed; with the aim to identify the concentration provided by the Test formulation, the basal status of each volunteer was eliminated from the analysis, which was built with 3 former concentrations to the test medicine administration. The analytical method used in this study was high resolution liquid chromatography with tandem mass spectrometry detector, HPLC MS/MS, for plasma Isotretinoin identification and quantification. The main pharmacokinetic parameters for the Test Product vs. the Reference Product were Tmáx 2.6 vs. 2.8 h, Cmáx 190.5 vs. 186.5 ng/mL for the AUC0-t 3003.8 vs. 2933.5 h* ng/mL and AUC0-∞ 3726.3 vs. 3521.2 h* ng/mL. The confidence interval calculation of data with logarithmic transformation, showed confidence intervals for the variables Tmáx, Cmáx, AUCo-t and AUCo-∞, with values between 80-125; values approved by the FDA and EMA European Medicines Agency, in their Bioavailability and Bioequivalence Guides, to accept the Bioequivalence hypothesis between the two formulations in study, and thereby declare Bioequivalence and interchange ability of the Test Product from Procaps Laboratory, with the Reference Product from Roche Laboratory