Inhibition of the oxidative metabolism of theophylline in isolated rat hepatocytes by the quinolone antibiotic enoxacin and its metabolite oxoenoxacin, but not by ofloxacin.
Isolated rat hepatocytes obtained from Aroclor-pretreated rats were incubated with theophylline in the presence or absence of the quinolone antibiotics enoxacin, its metabolite oxoenoxacin, or ofloxacin. The hepatocytes converted theophylline by cytochrome P-450 activity mainly to two metabolites: 1,3-dimethyluric acid and 3-methylxanthine. Enoxacin inhibited the formation of 1,3-dimethyluric acid by 67% at 1.0 mM. Oxoenoxacin or ofloxacin had no inhibitory effect. The oxidation of theophylline to 3-methylxanthine was not inhibited by any of the three compounds. The quinolones had no effect on cell viability. These results show that the inhibition by enoxacin is not due to the formation of its oxoenoxacin metabolite.
Mulder
G J
GJ
Division of Toxicology, University of Leiden, The Netherlands.
Nagelkerke
J F
JF
Tijdens
R B
RB
Wijnands
W J
WJ
Van der Mark
E J
EJ
D000818:Animals; D015365:Enoxacin; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D015242:Ofloxacin; D010078:Oxazines / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000378:metabolism*
D009287:Naphthyridines; D010078:Oxazines; D011804:Quinolines; D015365:Enoxacin; D015242:Ofloxacin; D013806:Theophylline