INFLUENCE OF CIGARETTE-SMOKING AND SEX ON THEOPHYLLINE DISPOSITION

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Abstract
The effects of cigarette smoking and sex on theophylline [a bronchodilator] clearance, elimination rate constant and apparent volume of distribution were examined in 28 healthy, young adults given single oral doses of theophylline or aminophylline. Two-way analysis of variance showed no sex effect but a significant effect of smoking habit on theophylline clearance and elimination rate constant. Neither sex nor smoking had an effect on the apparent volume of distribution. The respective mean clearance, elimination rate constant and volume of distribution were, in nonsmokers, 0.040 .+-. 0.008 (SD) l/h per kg, 0.084 .+-. 0.015 h-1, 0.47 .+-. 0.08 l/kg; heavy smokers, 0.063 .+-. 0.019 l/h per kg, 0.129 .+-. 0.045 h-1, 0.50 .+-. 0.06 l/kg and ex-smokers, 0.051 .+-. 0.10 l/h per kg, 0.108 .+-. 0.025 h-1, 0.49 .+-. 0.08 l/kg. Cigarette smoking apparently induced theophylline metabolism as reflected by the mean theophylline half-life in smokers (5.4 h) vs. nonsmokers (8.3 h). The effect of cigarette smoking on theophylline clearance may be an important consideration in the clinical use of the drug.