PT  - JOURNAL ARTICLE
AU  - U Fuhr
AU  - T Wolff
AU  - S Harder
AU  - P Schymanski
AU  - A H Staib
TI  - Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes.
DP  - 1990 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1005--1010
VI  - 18
IP  - 6
4099  - http://dmd.aspetjournals.org/content/18/6/1005.short
4100  - http://dmd.aspetjournals.org/content/18/6/1005.full
SO  - Drug Metab Dispos1990 Nov 01; 18
AB  - Inhibitory effects of the quinolone antibiotics ofloxacin, lomefloxacin, pipemidic acid, ciprofloxacin, and enoxacin on caffeine metabolism were examined in vitro with human liver microsomes of four donors. All drugs competitively inhibited the activity of 3-demethylation, the major pathway of caffeine metabolism. Enoxacin, ciprofloxacin, and pipemidic acid were strong inhibitors exhibiting Ki values between 0.1 and 0.2 mM. Lomefloxacin and ofloxacin had moderate effects with Ki values of 1.2 and 3.6 mM, respectively. The rate of caffeine 7-demethylation (which amounted to about 25% of that for 3-demethylation) was only slightly affected by the quinolones. Minor, but inconsistent, effects were found on 8-oxidation to 1,3,7-trimethyluric acid. The results indicate that the reduction of caffeine clearance by concomitant quinolone application observed in vivo is primarily due to a competitive interaction of the inhibiting quinolones with the cytochrome P-450 isoenzyme(s) mediating caffeine demethylation.