INDIVIDUAL AND COMBINED EFFECTS OF CIMETIDINE AND CIPROFLOXACIN ON THEOPHYLLINE METABOLISM IN MALE NONSMOKERS

1 The individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism were examined in six young male nonsmokers. 2 Treatment sequence consisted of 7 days each of cimetidine 400 mg p. o. every 12 h, ciprofloxacin 500 mg p.o. every 12 h, and the combinati on of cimetidine and ciprofloxacin. 3 Studies of theophylline pharmaco kinetics were performed at baseline and on the fifth day of each regim en. 4 Individually, cimetidine and ciprofloxacin decreased the clearan ce of theophylline by 25% and 32%, respectively. Therapy with the comb ined regimen resulted in a 41% reduction in theophylline clearance, wh ich was greater than that achieved with each drug alone (P < 0.01). 5 Ciprofloxacin, in contrast to cimetidine, inhibited N-demethylations o f theophylline to a significantly greater extent than the hydroxylatio n pathway. Combined treatment produced a further decline in formation of 1,3-dimethyluric acid than each drug alone. 6 These data suggest th at coadministration of cimetidine and ciprofloxacin exerts a greater i mpairment of theophylline biotransformation than each inhibitor alone. The enhanced inhibitory effect from the two inhibitors will occur onl y when sub-maximal doses of each individual agent are used.