Pharmacokinetics and Bioequivalence of Two Formulations of Letrozole 2.5 mg Tablets: A Randomized, Open-Label, Single-Dose, Two-period, Parallel Study in Healthy Chinese Subjects Recipients

Abstract

Objective: To evaluate the pharmacokinetics and bioequivalence of a generic (test) and branded (reference) formulation of letrozole 2.5 mg tablets in healthy Chinese volunteers to meet the criteria for marketing the test drug in China. Method: The current study was a randomized, open-label, single-dose, one-period, parallel test under fasted conditions in 26 healthy Chinese female and male volunteers. Blood was sampled at baseline (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post-dose from subjects randomly had reference or test drugs, respectively. Vital signs including temperature, blood pressure and heart rate were measured before and after dosing. Adverse events were recorded throughout the study. Plasma concentrations of letrozole were determined using a validated LC/MS/MS method. The primary pharmacokinetic parameters, Cmax , Tmax , AUC0-t , AUC0-inf were calculated for comparison of bioequivalence between the test (T) and reference (R) medications. Results: All 26 subjects (19 female, 7 male; mean age, 24 years [range, 21-29 years]; weight, 57.5 kg [range, 49.0-67.5 kg]) completed the study and data from them were included for comparison followed. The geometric mean Cmax for the test and reference formulations was 40.124 and 39.608 ng/mL, respectively. The mean AUC0-t was 1,437.933 and 1,532.048 ng•h/mL and the mean AUC0-inf was 2,566.558 and 2,953.276 ng•h/mL. The geometric mean ratios (test:reference) for Cmax and AUClast were 1.01 and 0.93, respectively. And The 90% confidence intervals (CIs) of the ratio of AUClast and Cmax were ranging from 84.97% to 102.31% and 91.97% to 111.30%, respectively. Conclusion: Our study on healthy fasted volunteers shows the test letrozole formulation of 2.5 mg tablets and reference formulation are bioequivalent. Keywords: