Effect of smoking on theophylline disposition

The pharmacokinetics of theophylline were examined in a group of nonsmokers and in heavy smokers (1 to 2 packs/day) before and 3 to 4 mo after cessation of cigarette smoking. The half-life of theophylline in smokers averaged 4.3 (SD = 1.4) hr, significantly shorter than the mean value in nonsmokers (7.0, SD = 1.7 hr). The apparent volume of distribution of theophylline was somewhat larger in smokers (0.50 ± 0.12 Llkg) than in nonsmokers (0.38 ± 0.04 Llkg). The body clearance of theophylline was appreciably larger and relatively more variable in smokers (100 ± 44 ml/min/1.73 m2) than in nonsmokers (45 ± 13 ml/min/1.73 m2). Serum concentrations of thiocyanate, a biotransformation product of cyanide which is inhaled with smoke, were used to monitor the smoking status of the subjects. The body clearances of theophylline showed a good correlation (r = 0.785, p < 0.001) with the serum thiocyanate concentrations. Of the 8 smokers, only 4 managed to refrain from smoking for at least 3 mo, and these subjects showed no significant change in theophylline elimination. The increase in theophylline clearance caused by smoking is probably the result of induction of drug-metabolizing enzymes that do not readily normalize after cessation of smoking.