Pharmacokinetic Comparison of Two Formulations of Erlotinib Hydrochloride Tablets in Healthy Volunteers

초록

Background: Erlotinib is an inhibitor of epidermal growth factor receptor tyrosine kinase used in the treatment of non-small cell lung cancer and pancreatic cancer. This study was conducted to compare the safety and pharmacokinetic profile of a new erlotinib generic formulation (Erlotinib tablets 150 mg, Samyang Biopharmaceuticals Co.) with those of the reference product (Tarceva®, Roche Korea Co., Ltd.) in healthy volunteers. Methods: A randomized, open-label, single-dose, two-treatment, two-sequence, two-period, crossover study was conducted in 40 healthy volunteers. Blood samples were obtained over 60 hours post-dose and plasma erlotinib concentrations were determined using a validated liquid chromatography-tandem mass spectrometry. There was a 14-day washout between periods. Pharmacokinetic parameters of the two formulations were calculated by non-compartmental analysis. Tolerability was evaluated throughout the study. Results: Forty male volunteers were enrolled and thirty-eight subjects completed the study. Median times to peak concentration of two formulations were 2.5 hour. The means [SD] of Cmax and AUC0-t were 1132.04 [352.76] ng/mL and 20598.30 [5190.28] hr•ng/mL for test formulation and 1089.89 [327.12] ng/mL and 20657.85 [5399.51] hr•ng/mL for the reference. Geometric mean ratios (90 % confidence intervals) for the test to the reference were 1.03 (0.95-1.11) for Cmax and 1.00 (0.93-1.06) for AUC0-t. A total of 40 cases of adverse events were reported (19 on test formulation, 21 on reference formulation) in 21 subjects. The most frequent adverse events were 20 occurrences of rash acneiform in 12 subjects. Both formulations were well tolerated and there were no serious adverse event. Conclusion: The test and reference formulations demonstrated similar pharmacokinetic profiles. The test formulation of erlotinib met the Korean regulatory criteria for bioequivalence.