Effects of Smoking on the Pharmacokinetics of Erlotinib

Abstract

Purpose: To compare the pharmacokinetic variables of erlotinib in current smokers with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib. Experimental Design: This was a single-center, open-label pharmacokinetic study in healthy male subjects. Subjects were enrolled into two treatment cohorts based on smoking status (current smokers and nonsmokers). The pharmacokinetic profile for erlotinib and its metabolite, OSI-420, was determined for each subject following each treatment. Results: Current smokers achieved significantly less erlotinib exposure following a single 150 or 300 mg dose than nonsmokers. Following the 150 mg dose, the geometric mean erlotinib AUC_0-∞ in smokers was 2.8-fold lower than in nonsmokers and similar to that of nonsmokers at the 300 mg dose. C_max in smokers was two-thirds of that in nonsmokers, and C_24h in smokers was 8.3-fold lower than in nonsmokers. The median C_24h of smokers at the 300 mg dose was slightly less than the C_24h of smokers at the 150 mg dose. The median C_max was greater in smokers at the 300 mg dose than in nonsmokers at the 150 mg dose. Conclusion: This study confirms that the pharmacokinetics of erlotinib is different in current smokers and nonsmokers. The observation that AUC_0-∞ and C_24h were significantly decreased in smokers compared with nonsmokers, and a smaller decrease in C_max was observed, is consistent with increased metabolic clearance of erlotinib in current smokers.