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Effect of smoking on theophylline disposition
Author(s) -
Hunt Susan N.,
Jusko William J.,
Yurchak Anthony M.
Publication year - 1976
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1976195part1546
Subject(s) - theophylline , volume of distribution , pharmacokinetics , thiocyanate , medicine , caffeine , chemistry , pharmacology , biochemistry
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 Llkg). The body clearance of theophylline was appreciably larger and relatively more variable in smokers (100 ± 44 ml/min/1.73 m 2 ) than in nonsmokers (45 ± 13 ml/min/1.73 m 2 ). 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.