Effects of Smoking on the Pharmacokinetics of Erlotinib

• Published in: Clinical cancer research Vol. 12; no. 7; pp. 2166 - 2171
• Main Authors: HAMILTON, Marta, WOLF, Julie L, RUSK, Jason, BEARD, Shannon E, CLARK, Gary M, WITT, Karsten, CAGNONI, Pablo J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2006
• Subjects: Adult; Antineoplastic agents; Area Under Curve; Biological and medical sciences; Cohort Studies; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; epidermal growth factor receptor; erlotinib; Erlotinib Hydrochloride; Humans; lung cancer; Male; Medical sciences; Middle Aged; Molecular Structure; pharmacokinetics; Pharmacology. Drug treatments; Quinazolines - administration & dosage; Quinazolines - pharmacokinetics; Reference Values; Safety; Smoking; Time Factors; Tobacco, tobacco smoking; Toxicology; Antineoplastic agent; Erlotinib; Enzyme; Quinazoline derivatives; Transferases; Tobacco smoking; Enzyme inhibitor; Pharmacokinetics; Protein-tyrosine kinase; Epidermal growth factor receptor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2235

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.