Comparison of Inhibitory Effects of New Quinolones on Drug Metabolizing Activity in the Liver

Abstract

The effects of three new quinolones (enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX)) on acetaminophen-induced liver injury in rats were examined and compared with their effects on the elimination half-life (T1/2) of theophylline (in vivo) and on the 7-ethoxycoumarin (7-EC) O-deethylase activity in liver microsomes (in vitro). ENX, NFLX and OFLX (75 or 300 mg/kg) were administered orally to rats 1 hr before, simultaneously with, and 1 hr after the acetaminophen injection (800 mg/kg). Biochemical liver function tests, drug metabolizing activity in liver microsomes, the total glutathione content of the liver and histological changes were examined 5 hr after the acetaminophen injection. ENX markedly reduced acetaminophen-induced liver injury and NFLX slightly but significantly did so, but no protective effect was observed with OFLX treatment. ENX markedly and NFLX slightly prolonged the T1/2 of theophylline, but OFLX did not affect it. In addition, ENX markedly and NFLX slightly inhibited the 7-EC O-deethylase activity in liver microsomes, but OFLX again had no effect. These findings indicated that ENX markedly inhibited the activity of cytochrome P-450 in liver microsomes and NFLX did so slightly, while OFLX had no such effect. Slight variations in the structures of these quinolones might explain the differences in their effects on cytochrome P-450 activity.