Theophylline-rifampicin interaction: non-selective induction of theophylline metabolic pathways.
The effect of rifampicin pre-treatment (600 mg daily for 6 days) on theophylline disposition at steady state was investigated in six healthy males. Following rifampicin treatment total plasma clearance of theophylline increased by 82%. Theophylline clearance through each metabolic pathway was increased, 1-demethylation by (116 +/- 34%) (mean +/- s.e. mean), 3-demethylation by (91 +/- 16%) and 8-oxidation by (81 +/- 17%). Renal clearance of unchanged drug was not altered. Previous studies have suggested that two forms of cytochrome P-450 are involved in theophylline metabolism, one mediating the N-demethylations and the other 8-oxidation. Thus, unlike the selective inductive effect of rifampicin on antipyrine metabolic pathways, rifampicin does not differentially affect those forms of cytochrome P-450 involved in theophylline metabolism. The extent to which theophylline metabolism is induced by rifampicin is likely to have important clinical consequences.
D000328:Adult; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D004347:Drug Interactions; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D012293:Rifampin / Q000494:pharmacology*; D013806:Theophylline / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D012293:Rifampin