Effect of New Quinolones on Drug-Metabolizing Enzyme System of Rat Hepatic Microsomes

Abstract

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 b₅and NADPH-cytochrome P-450 reductase and in the activity of ethoxycou-marin O-deethylase, and significant decreases in the activities of benzphetamine N-de-methylase 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.

Marek's disease vaccination, with turkey herpesvirus, and enrofloxacin modulate the activities of hepatic microsomal enzymes in broiler chickens

“…Although many studies performed by others have shown that ENR and other quinolones mainly inhibited hepatic cytochrome P450 enzyme activities, there are also a few references about their inductive, or even no, effect on cytochrome P450 dependent monooxygenase system, e.g. in rats (Okazaki et al, 1988;Vancustem and Babish, 1996). We found here that in chickens vaccinated with HVT activities of both enzymes increased with increasing dose.…”

Side-effects of quinolones: Comparisons between quinolones and other antibiotics

“…This interaction is probably not due to the cytochrome P-450 system since rat studies have failed to detect any type of interaction with that system (14). Most quinolones are metabolised in the liver, although to a varying dedegree.…”

Quinolones: a class of antimicrobial agents

“…Ciprofloxacin administration over a period of 8-10 days prolonged the half-life of antipyrine from 9.45 to 14.9 h attributed to decreased clearance from 0.85 to 0.52 ml/min/ kg in human patients (Ludwig et al, 1988). However, others have stated that oral doses of ofloxacin, enoxacin and norfloxacin showed no significant effect on the content of cytochrome P450, cytochrome b 5 , NADPH-cytochrome P450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase, or aniline hydroxylase in phenobarbital-responsive systems (Okazaki et al, 1988). Furthermore, the clinically important drug-drug interactions between theophylline and ofloxacin were not shown in several instances .…”