Effect of new quinolones on drug-metabolizing enzyme system of rat hepatic microsomes.
Effects of repeated oral administration of new quinolones, ofloxacin, enoxacin and norfloxacin, once daily for 7 days, on the drug-metabolizing enzyme system of rat hepatic microsomes were studied in comparison with that of phenobarbital, a potent inducer of cytochromes P-450. Treatment of phenobarbital at the oral dose of 120 mg/kg induced significant increases in the contents of cytochrome P-450, cytochrome b5 and NADPH-cytochrome P-450 reductase and in the activity of ethoxycoumarin O-deethylase, and significant decreases in the activities of benzphetamine N-demethylase and aniline hydroxylase. However, ofloxacin, enoxacin and norfloxacin at the oral dose levels of 80 and 320 mg/kg showed no significant effect on the content of each constituent of the drug-metabolizing enzyme system, and the three enzyme activities. Thus, it is concluded that new quinolones including ofloxacin have no ability to induce a cytochrome-P-450-dependent monooxygenase system.
Okazaki
O
O
Drug Metabolism Research Center, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Kurata
T
T
Tachizawa
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015365:Enoxacin; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009287:Naphthyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D009643:Norfloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D015242:Ofloxacin; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D009287:Naphthyridines; D010078:Oxazines; D015365:Enoxacin; D003577:Cytochrome P-450 Enzyme System; D015242:Ofloxacin; D009643:Norfloxacin