Pharmacokinetic Comparison of Two Formulations of Letrozole 2.5mg Tablets in Healthy Volunteers

초록

Background: This study was conducted to compare the bioavailability of a new letrozole generic formulation (Letrozole tablet 2.5 mg, Teva-Handok Pharma Co., Ltd.) with those of the reference product (Femara®, Novartis Korea Co., Ltd.) in healthy volunteers. Methods: A randomized, open-label, single-dose, two-treatment, two-sequence, two-period, crossover study was conducted in 34 healthy volunteers. Blood samples were obtained at 0, 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.33, 2.67, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours after drug administration. There was a 42-day washout between periods. Pharmacokinetic parameters of the two formulations were calculated by non-compartmental analysis. Tolerability was evaluated throughout the study. Results: Twenty-nine subjects completed the study. A total of eight cases of adverse events (AEs) were reported (2 on test formulation, 6 on reference formulation) in five subjects. These AEs were alopecia (n=2), urticaria (n=2), pruritis (n=2), dizziness (n=1), and vasovagal reaction (n=1). Both formulations were well tolerated and there were no serious adverse event. The mean [SD] of Cmax were 37.85 [9.80] ng/mL for test formulation and 38.48 [8.97] ng/mL for the reference; the mean [SD] AUC0-t were 1076.69 [249.25] ng•hr/mL and 1077.56 [246.96] ng•hr/mL, respectively; and the median Tmax were 1.67 hours and 1.33 hours, respectively. The geometric mean ratios (90 % confidence intervals) for the test to the reference were 0.98 (0.89-1.07) for Cmax and 1.00 (0.98-1.02) for AUC0-t. Conclusion: The test and reference formulations demonstrated similar pharmacokinetic profiles. The test formulation of letrozole met the Korean regulatory criteria for bioequivalence.