Hamilton Marta, Wolf Julie L, Rusk Jason, Beard Shannon E, Clark Gary M, Witt Karsten, Cagnoni Pablo J
OSI Pharmaceuticals, Inc., Boulder, Colorado, USA.
Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. doi: 10.1158/1078-0432.CCR-05-2235.
To compare the pharmacokinetic variables of erlotinib in current smokers with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib.
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.
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.
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.
比较当前吸烟者与非吸烟者在单次口服150或300毫克厄洛替尼后的药代动力学变量。
这是一项在健康男性受试者中进行的单中心、开放标签的药代动力学研究。根据吸烟状况（当前吸烟者和非吸烟者）将受试者纳入两个治疗队列。在每次治疗后，测定每位受试者的厄洛替尼及其代谢物OSI-420的药代动力学特征。
在单次服用150或300毫克剂量后，当前吸烟者的厄洛替尼暴露量明显低于非吸烟者。服用150毫克剂量后，吸烟者中厄洛替尼的几何平均AUC(0-无穷大)比非吸烟者低2.8倍，与服用300毫克剂量的非吸烟者相似。吸烟者的C(max)是非吸烟者的三分之二，吸烟者的C(24小时)比非吸烟者低8.3倍。300毫克剂量吸烟者的C(24小时)中位数略低于150毫克剂量吸烟者的C(24小时)。300毫克剂量吸烟者的C(max)中位数大于150毫克剂量非吸烟者的C(max)。
本研究证实了当前吸烟者和非吸烟者中厄洛替尼的药代动力学不同。与非吸烟者相比，吸烟者的AUC(0-无穷大)和C(24小时)显著降低，且C(max)降低幅度较小，这一观察结果与当前吸烟者中厄洛替尼代谢清除增加一致。
