Pharmacokinetic and bioequivalence study of endogenous compound tretinoin 10 mg capsules in healthy volunteers by base line correction approach

Abstract

Tretinoin belongs to the class of retinoids indicated in induction of remission in acute promyelocytic leukemia (APL-FAB classification AML-M3). It is an endogenous metabolite of Vitamin A and is normally present in human plasma. The objective of the present study was to evaluate the bioequivalence between the Tretinoin 10 mg capsules of Ranbaxy Laboratories Limited and VESANOID® 10 mg capsules of Roche Pharmaceuticals Inc. It was a 2-way cross-over single dose study in 60 adult Indian male volunteers under fasting conditions. Since tretinoin is endogenously present in the human body, for baseline adjustment four pre-dose samples were collected. Plasma samples were analyzed for tretinoin by using validated liquid chromatographic mass spectrometry (LC-MS/MS) method. This method has separated both isomeric metabolites (i.e. isotretinoin and 9-oxo retinoic acid) from tretinoin to accurately measure the tretinoin concentrations in plasma for this study. The Mean ± SD of pharmacokinetic parameters Tmax, Cmax, and AUC0−t for tretinoin were 2.55 ± 0.84 and 2.40 ± 0.86 h, 34.29 ± 10.45 and 32.77 ± 9.16 ng/ml, 87.28 ± 30.99 and 80.81 ± 24.68 ng.h/ml, respectively, for test and reference. The ratios of least square means and its 90% confidence interval for Cmax, AUC0−t and AUC0–∞ on both baseline corrected and uncorrected data were found to be within 80–125%.