吸烟与茶碱代谢：苯妥英的影响。

Cigarette smoking and theophylline metabolism: effects of phenytoin.

作者信息

Crowley J J, Cusack B J, Jue S G, Koup J R, Vestal R E

出版信息

Clin Pharmacol Ther. 1987 Sep;42(3):334-40. doi: 10.1038/clpt.1987.157.

DOI:10.1038/clpt.1987.157

Abstract

The induction of theophylline clearance by phenytoin was investigated in 12 young male subjects (six nonsmokers and six cigarette smokers). Each subject received intravenous theophylline to determine baseline pharmacokinetics. This was followed by an intravenous loading dose of phenytoin sodium and oral maintenance dosing for 2 weeks, after which the intravenous theophylline study was repeated. Phenytoin concentrations were similar in nonsmokers (10.8 +/- 2.0 micrograms/ml) and smokers (11.5 +/- 0.9 micrograms/ml). Control theophylline elimination half-life was 35% less and clearance 88% greater in smokers than in nonsmokers. The proportionate changes in half-life (26.8% +/- 5.6% in smokers and 25.8% +/- 3.5% in nonsmokers) and clearance (48.0% +/- 10.1% in smokers and 39.7% +/- 7.2% in nonsmokers) as the result of phenytoin induction were similar in both groups. These results demonstrate that the induction of theophylline clearance by phenytoin is additive to that caused by cigarette smoking and provide support for the suggestion that theophylline metabolism is influenced by multiple polymorphisms.

摘要

在12名年轻男性受试者（6名不吸烟者和6名吸烟者）中研究了苯妥英对茶碱清除率的诱导作用。每位受试者接受静脉注射茶碱以确定基线药代动力学。随后静脉注射苯妥英钠负荷剂量并口服维持剂量2周，之后重复静脉注射茶碱研究。不吸烟者（10.8±2.0微克/毫升）和吸烟者（11.5±0.9微克/毫升）的苯妥英浓度相似。吸烟者的对照茶碱消除半衰期比不吸烟者短35%，清除率比不吸烟者高88%。两组中苯妥英诱导导致的半衰期（吸烟者为26.8%±5.6%，不吸烟者为25.8%±3.5%）和清除率（吸烟者为48.0%±10.1%，不吸烟者为39.7%±7.2%）的相应变化相似。这些结果表明，苯妥英对茶碱清除率的诱导作用与吸烟引起的作用相加，并支持茶碱代谢受多种多态性影响的观点。