生物学的同等性とバイオアベイラビリティのジャーナル

概要

The Affect of Capmul, Labrafil and Transcutol on Progesterone 100 Mg Soft Capsules Bioavaialbility in Indian Healthy Adult Postmenopausal Female Subjects Under Fasting Conditions

Rajeswara Rao P, Someswara Rao K and Subba Rao M

The aim of this study was to evaluate the affect of solubilizers of capmul, labrafil and transcutol on progesterone 100 mg soft capsules of two different Test batches (Test-1 and Test-2) in comparison with that of Prometrium® (Progesterone USP) capsules 100 mg of Reference Product of Abbott Laboratories, USA in healthy adult, human, post-menopausal female volunteers. This study was an open label, balanced, randomized, three treatment, six sequence, three period, cross-over, single-dose comparative oral bioavailability study of Progesterone USP capsules 100 mg of two different Test batches (Test-1 and Test-2) conducted in 18 healthy adult, human, post-menopausal female volunteers under fasting conditions. Subjects received progesterone 100 mg of either test (Test-1 and Test- 2) or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 24 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 T1/2were determined for both test (Test-1 and Test-2) and reference 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-∞ for baseline adjusted data, Cmax and AUC0-t for baseline unadjusted data were within the predetermined bioequivalence range of 80.00% to 125.00%. A total of 18 subjects were enrolled. No significant differences were found based on analysis of variance. The 90% confidence intervals (CI) for Cmax, AUC0-t and AUC0-∞of progesterone baseline adjusted data were 617.99-1488.02%, 270.11-683.70%, and 228.82-523.71% respectively. The 90% confidence intervals (CI) for Cmax and AUC0-t of progesterone baseline unadjusted data were 497.80-1180.16% and 156.81-407.82% respectively. Both the test formulations (Test-1 and Test-2) in this study were fails to show the bioequivalence with that of reference formulation for progesterone and were found to have significantly suprabioavailale. The intra subject variability (%) for Cmax, AUC0-t and AUC0-∞of progesterone baseline adjusted data were found to be 87.49%, 94.16% and 74.66% respectively. The intra subject variability (%) for Cmax and AUC0-t of progesterone baseline unadjusted data were found to be 85.47% and 97.93% respectively. There was a significant intra subject variability was observed for both the test formulations (Test-1 and Test-2) for progesterone under fasting conditions.