Effect of smoking on theophylline disposition

Clin Pharmacol Ther. 1976 May;19(5 Pt 1):546-51. doi: 10.1002/cpt1976195part1546.


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 L/kg) than in nonsmokers (0.38 +/-0.04 L/kg). 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 less than 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Male
  • Saliva / metabolism
  • Smoking*
  • Theophylline / blood
  • Theophylline / metabolism*
  • Thiocyanates / blood


  • Thiocyanates
  • Theophylline