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Cancer Therapy: Clinical |
Authors' Affiliation: OSI Pharmaceuticals, Inc., Boulder, Colorado
Requests for reprints: Marta Hamilton, OSI Pharmaceuticals, Inc., 2860 Wilderness Place, Boulder, CO 80301. Phone: 303-546-7788l; Fax: 303-444-0672; E-mail: mhamilton{at}osip.com.
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 AUC0-
in smokers was 2.8-fold lower than in nonsmokers and similar to that of nonsmokers at the 300 mg dose. Cmax in smokers was two-thirds of that in nonsmokers, and C24h in smokers was 8.3-fold lower than in nonsmokers. The median C24h of smokers at the 300 mg dose was slightly less than the C24h of smokers at the 150 mg dose. The median Cmax 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 AUC0- and C24h were significantly decreased in smokers compared with nonsmokers, and a smaller decrease in Cmax was observed, is consistent with increased metabolic clearance of erlotinib in current smokers.
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