RESUMEN
BACKGROUND: Erlotinib is a tyrosine kinase inhibitor prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. The aim of this study was to compare the safety and pharmacokinetics (PK) of a generic (test) formulation of erlotinib with those of a reference formulation in healthy volunteers. METHODS: A randomized, open-label, single-dose two-treatment, two-period, two-sequence, crossover study was conducted in Clinical Trials Center, Chungnam National University Hospital with 40 healthy men. Subjects orally received either one 150 mg tablet of the test or the corresponding dose of the reference, and crossover phases were separated by 14-day washout. Plasma samples were collected up to 72 hr post-dose. Plasma erlotinib concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated by non-compartmental analysis. The safety was monitored throughout the study. RESULTS: A total of 21 cases of adverse events were reported. They are mild and relieved without an intervention. There was no serious adverse event. Median times to peak concentration of two formulations were 3.0. Means [SD] for peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of the test were 1,298 [346] microg/L and 25,318 [7,668] hrxmicrog/L. Those of the reference were 1,193 [378] microg/L and 24,853 [8,419] hrxmicrog/L. Geometric mean ratios (90% confidence intervals) for the test to the reference were 1.10 (1.02-1.18) for Cmax and 1.02 (0.97-1.09) for AUC. CONCLUSION: Two formulations were safe and well-tolerated. PK findings suggest that the test formulation is equivalent to the reference in terms of pharmacokinetics.