Fluoroquinolone Drugs On The Nervous System, The Role Of Liver Drug Metabolizing Enzymes

Fluoroquinolones, a new type quinolones antibacterial agents with fluorin, are extensively used in the clinics because of its wide antibacterial spectrum and strong antibacterial activity. But its side-effect in the clinics can not be overlook. Fluoroquinolnes widely inhibit the activity of drug- metabolism enzymes in rats liver microsome (cytochrome P450, CYP450). The case, however, was a little to be reported on the humen liver microsome. This article studied on the effects of the fluoroquinolones, including ciprofloxacin, ofloxacin, levofloxacin and pefloxacin on the activity of drug-metabolism enzymes in humen liver microsome.Our objective is to know the difference in the effects of different fluoroquinolones on the activity of drug-metabolism enzymes (Benzo pyriene hydroxylase,Pentobarbital side chain hydroxylase,Aminopyrine N- demethylase,Ethylmorphine N-demethylase and NDAPH-cytochrome C reductase) in humen liver microsome. In our experiments in vitro, the final concentration of microsome protein was 1.0g/L and fluoroquinolones 400mg/L in the reaction system. The final concentrations of substrate were 0.5, 1.0, 2.0, 4.0, 8.0mmol/L and inhibitor 0, 50, 100, 200, 400mg/L in the enzyme kinetics experiment, respectively. The results showed that the activities of manifold drug-metabolism enzymes were inhibited by fluoroquinolones in some degree. The inhibited degree of fluoroquinolones on CYP450 activity are pefloxacin greater than ciprofloxacin than ofloxacin than levofloxacin. Enzyme kinetics indicates that there is mixed inhibition of ciprofloxacin on the ethylmorphine N-demethylase but competitive inhibition playsd an important role (Ki= 250mg/L), and the inhibition is dose-dependancy.