Effects of smoking on the pharmacokinetics of erlotinib.
OBJECTIVE
To compare the pharmacokinetic variables of erlotinib in current smokers with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib.


METHODS
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.


CONCLUSIONS
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.
Hamilton
Marta
M
OSI Pharmaceuticals, Inc., Boulder, Colorado, USA. mhamilton@osip.com
Wolf
Julie L
JL
Rusk
Jason
J
Beard
Shannon E
SE
Clark
Gary M
GM
Witt
Karsten
K
Cagnoni
Pablo J
PJ
D000328:Adult; D019540:Area Under Curve; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values; D012449:Safety; D012907:Smoking; D013997:Time Factors
C487471:OSI-420; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride