Effects of smoking on the pharmacokinetics of erlotinib.

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Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ

Effects of smoking on the pharmacokinetics of erlotinib.

Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71.

PubMed ID

16609030 [ View in PubMed

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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-infinity) 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-infinity) 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Erlotinib	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details
Erlotinib	Cytochrome P450 2C8	Protein	Humans	Unknown	Substrate Inhibitor	Details
Erlotinib	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details