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

Rajeswara Rao P and Someswara Rao K

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.