title: Differential effects of cimetidine on theophylline metabolic pathways.
abstract: The effects of cimetidine (1 g/day) on theophylline disposition and metabolism were examined in smokers and non-smokers for single dose intravenous and chronic oral administration of theophylline. In the intravenous study the effect of cimetidine on plasma theophylline clearance was more marked in smokers (22.7% reduction) than in non-smokers (12.2% reduction). Similarly, in the multiple dose study the effect of cimetidine on theophylline clearance was greater in smokers (28.3% decrease) than in non-smokers (11.3% decrease). The reduction in clearance was largely due to a reduction in metabolic clearances by 3-demethylation ( Cl3DM ) and 1-demethylation ( Cl1DM ) with no significant effect on clearance by 8-oxidation ( Cl80X ). There was a strong correlation between Cl3DM and Cl1DM (r = 0.98, p less than 0.001) in both control and cimetidine study phases, whereas other correlations between partial clearances were less marked and were not apparent during the cimetidine phase. The results are consistent with the view that 1- and 3-demethylation of theophylline are carried out by a common form of cytochrome P-450 which is selectively induced by cigarette smoking and preferentially inhibited by cimetidine.
mesh_terms: D000328:Adult; D002927:Cimetidine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D012907:Smoking; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D002927:Cimetidine; D013806:Theophylline