Selectivity and dose-dependency of the inhibitory effect of propranolol on theophylline metabolism in man.
The effects of separate 5 day pretreatments of propranolol 120 mg day-1 and 720 mg day-1 on theophylline clearance and metabolism at steady-state were determined in seven healthy males. Propranolol 120 mg day-1 decreased theophylline plasma clearance (CL) by 30%. Clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylated products by 42-43% and clearance to the 8-hydroxylation product by 27%. Propranolol 720 mg day-1 decreased theophylline CL by 52%. Again, clearance of theophylline to each metabolite was reduced by this treatment, clearances to the two demethylation products by 73-77% and clearance to the 8-hydroxylation product by 44%. These data are consistent with a dose-dependent and selective inhibitory effect of propranolol on the separate forms of cytochrome P-450 involved in theophylline demethylation and 8-hydroxylation.
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003640:Dealkylation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D013806:Theophylline / Q000097:blood / Q000378:metabolism*
D065607:Cytochrome P-450 Enzyme Inhibitors; D011433:Propranolol; D013806:Theophylline