Intra Subject Variability of Progesterone 200 mg Soft Capsules in Indian Healthy Adult Postmenopausal Female Subjects under Fasting Conditions

Abstract

The aim of this study was to evaluate the intra subject variability of progesterone 200 mg soft capsules of Test product with Prometrium® (Progesterone USP) capsules 200 mg (Reference) marketed by Solvay Pharmaceuticals Inc., Marietta, GA in healthy adult, human, post-menopausal female volunteers. This study was an open label, randomized, balanced, single-dose, two sequence two period, crossover oral bioequivalence study was conducted in 12 healthy adult, human, post-menopausal female volunteers under fasting conditions. Subjects received progesterone 200 mg of either test or reference formulation with a washout period of 10 days. After study drug administration, serial blood samples were collected over a period of 36 hours post dose. The plasma concentrations of progesterone were determined by a validated method using LC/MS/MS. Pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, Kel and T1/2 were determined for both the formulations. The formulations were to be considered bioequivalent if the geometric least square mean ratio of test and reference of Cmax, AUC0-t and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 12 subjects were enrolled. No significant differences were found based on analysis of variance. The 90% confidence intervals (CI) of Cmax, AUC0-t and AUC0-∞, of progesterone were 52.10-148.80%, 52.66-164.84%, and 56.05-152.68% respectively. The test formulation in this study fails to show the bioequivalence with that of reference formulation for progesterone. The intra subject variability (%) for Cmax, AUC0-t and AUC0-∞ were found to be 68.2, 75.6 and 64.6 respectively. There was significant intra subject variability was observed for progesterone under fed conditions.