Differences in the hepatobiliary transport of two quinolone antibiotics, grepafloxacin and lomefloxacin, in the rat

The biliary excretion of grepafloxacin (GPFX) was compared with that of lom efloxacin (LFLX) in rats. The biliary clearances (Cl-bile(plasma)) of GPFX was 2.9 times greater than LFLX based on the plasma concentration reached d uring constant intravenous (iv) infusion. The liver-plasma unbound concentr ation ratio, K-pu, of GPFX (1.7) was also higher than that of LFLX (0.7). T he hepatic uptake clearance, assessed from an integration plot analysis, of GPFX was comparable with the hepatic blood flow rate, and 1.5 times that o f LFLX, indicating that membrane transport in the uptake process is more ef ficient for GPFX. This was also supported by the difference between the upt ake clearance of GPFX and LFLX in isolated rat hepatocytes. The bile-liver unbound concentration ratio of GPFX and LFLX was approximately 6 and 3, res pectively, and the biliary clearance based on the unbound Liver concentrati on of GPFX was 1.8 times that of LFLX. These results suggest that the conce ntrative transport of GPFX also across the canalicular membrane was more ef ficient than that of LFLX. Thus, the membrane transport activity via both s inusoidal and canalicular membranes determines the net excretion of each co mpound. Copyright (C) 1999 John Wiley & Sons, Ltd.