Bioequivalence study of two formulations containing isotretinoin in fed condition in Colombian healthy volunteers

This is a pharmacokinetic trial that evaluates under fed conditions two formulations containing 20 mg of Isotretinoin, with the aim to compare the Bioavailability, between the Test Product (Isoface® Isotretinoin from Procaps S.A. Laboratory, Colombia) and the Reference Product (Roaccutane® Isotretinoin from Catalent Germany Laboratory, Eberbach GMBH, Germany.), to be able to declare Bioequivalence between both formulations.The same formulations were previously studied by these authors under fasting conditions.For this trial, an open, cross-over, randomized study of two periods and two sequences was carried out, with a single dose of 40 mg of Isotretinoin in fed conditions, in 28 healthy male volunteers; washing period was 14 days between each period.For results presentation, Plasma concentration ratio Vs Time curves were runned until hour 72.In order to identify the concentration provided by the studied formulation, the baseline status of each volunteer which was constructed with 3 concentrations prior to the administration of the study drug was eliminated from the analysis.The analytical method employed was high performance liquid chromatography with tandem mass spectrometry detector, HPLC MS/MS, for identification and quantification of Isotretinoin in plasma.The main pharmacokinetic parameters for the Reference Product Vs the Test Product were: T max 5.3 Vs 5.6hours, C max 374.6 Vs 385.1ng/ mL, AUC 0-t 6421.3Vs 6590.0hr*ng/mL and AUC 0-inf 7484.9Vs 7233.2hr*ng/mL.Confidence interval calculation of data with logarithmic transformation showed confidence intervals for the variables C max , AUC o-t , and AUC 0-Inf within the values 80-125%, accepted by the F.D.A. and by the European Medicines Agency EMA in their bioavailability and bioequivalence guidelines to accept the Bioequivalence hypothesis between the two formulations under study, and thus, declare Bioequivalence and interchangeability of the Procaps S.A. Laboratory product (Test Product), with the Catalent Germany Laboratory, Eberbach GMBH product (Reference Product).