Dong S X, Ping Z Z, Xiao W Z, Shu C C, Bartoli A, Gatti G, D'Urso S, Perucca E
Institute of Clinical Pharmacology, Great Chinese Wall Hospital, Beijing, People's Republic of China.
Ther Drug Monit. 1998 Aug;20(4):371-5. doi: 10.1097/00007691-199808000-00002.
The effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition was evaluated in a controlled study of 36 healthy Chinese subjects. Each subject was administered a single oral dose of phenacetin (900 mg), and frequent blood samples were taken for up to 12 hours for simultaneous high-pressure liquid chromatography determinations of plasma concentrations of phenacetin and metabolically derived paracetamol. Compared with values observed in controls not exposed to cigarette smoking, subjects who smoked 7 to 40 (median, 20) cigarettes per day exhibited a 2.5-fold higher phenacetin apparent oral clearance (7.2, 4.3-12.0 L x h(-1) x kg(-1) vs 2.9, 1.8-4.6 L x h(-1) x kg(-1) [geometric means, 95% confidence intervals]; n = 12, p < 0.05). In subjects exposed to passive smoking, phenacetin's apparent oral clearance (3.6, 2.0-46.6 L x h(-1) x kg(-1), n = 12) was intermediate between the values observed in the two other groups. Plasma paracetamol levels were moderately lower in active smokers than in passive smokers and controls. These results demonstrated that, in contrast to results found in previous studies, Chinese subjects were fully susceptible to the inducing effect of cigarette smoke on CYP1A2 activity.
在一项针对36名健康中国受试者的对照研究中，评估了主动吸烟和被动吸烟对CYP1A2介导的非那西丁代谢的影响。每位受试者口服单次剂量的非那西丁（900毫克），并在长达12小时内频繁采集血样，用于同时通过高压液相色谱法测定血浆中非那西丁及其代谢产物对乙酰氨基酚的浓度。与未接触吸烟的对照组相比，每天吸食7至40支（中位数为20支）香烟的受试者非那西丁的表观口服清除率高出2.5倍（7.2，4.3 - 12.0L×h⁻¹×kg⁻¹ vs 2.9，1.8 - 4.6L×h⁻¹×kg⁻¹[几何均值，95%置信区间]；n = 12，p < 0.05）。在接触被动吸烟的受试者中，非那西丁的表观口服清除率（3.6，2.0 - 46.6L×h⁻¹×kg⁻¹，n = 12）介于其他两组观察值之间。主动吸烟者血浆中对乙酰氨基酚水平略低于被动吸烟者和对照组。这些结果表明，与先前研究结果相反，中国受试者对香烟烟雾诱导CYP1A2活性的作用完全敏感。
