AIM:To observe the difference of effects of fluoroquinolones, including ciprofloxacin, ofloxacin, levofloxacin and pefloxacin on the activity of drug metabolism enzymes (cytochrome P 450) in human liver microsomes. METHODS: In vitro , the final concentration of microsomes protein was 0.33 - 2.0 g·L -1 and that of fluoroquinolones was 400 mg·L -1 in the reaction system. There were no drugs in contrast groups. The activity of drug metabolism enzymes was determined. The V m and K m of ethylmorphine N demethylase was respectively determined in the different concentrations of substrate and ciprofloxacin in the enzymatic kinetics experiment. RESULTS: The activities of manifold drug metabolism enzymes (CYP 450) were inhibited by fluoroquinolones on the different degree. The capability and activity of drug metabolism enzymes inhibited by fluoroquinolones were as follows. Those of pefloxacin were greater than those of ciprofloxacin, Those of ciprofloxacin were greater than those of ofloxacin, Those of ofloxacin were greater than those of levofloxacin. The mean inhibitive rates of fluoroquinolones to pentobarbital side chain hydroxylase, benzopyrene hydroxylase, aminopyrine N demethylase, ethylmorphine N demethylase, and NADPH cytochrome C reductase were 29 %, 26 %, 19 %, 17 % and 2.
3 % , respectively. Enzyme kinetics of ethylmorphine N demethylase indicated that inhibition of the ciprofloxacin on the activity was mixed, but competitive inhibition played an important role ( K i =250 mg· L -1 ). CONCLUSION:The activity of manifold drug metabolism enzymes can be inhibited by four fluoroquinolones on the different degree, and the inhibitory ability of levofloxacin is relatively weaker than that of others. The sensitivity of five drug metabolism enzymes to fluoroquinolones are different too, and the activity of NADPH cytochrome C reductase is almost not inhibited. The inhibition of the ciprofloxacin on the activity of ethylmorphine N demethylase is mixed, and competitive inhibition plays an important role.