EFFECT OF A BACTERIAL LIPOPOLYSACCHARIDE ON BILIARY-EXCRETION OF A BETA-LACTAM ANTIBIOTIC, CEFOPERAZONE, IN RATS

Klebsiella pneumoniae O3 lipopolysaccharide (LPS) has been found to dr amatically modify the pharmacokinetics of the p-lactam antibiotic cefa zolin in rats. This study investigated the effect of LPS on the biliar y excretion of the p-lactam antibiotic cefoperazone (CPZ) in rats. CPZ is known to be actively secreted into the bile by a carrier-mediated transport system. LPS (250 mu g/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CPZ (20 mg/kg). The pharmacokinetic parameters of CPZ were estimated by a noncompartme nt model. LPS induced a significant decrease in the systemic clearance (by approximately 50%) and an increase in the mean residence time of CPZ. Significant decreases were also seen in the bile flow rate and in the biliary recovery of unchanged CPZ in the LPS-treated rats. LPS te nded to increase the proportion of urinary excretion of CPZ. LPS signi ficantly decreased the biliary clearance (by approximating 55%) and re nal clearance (by approximately 35%) of CPZ. However, no changes in th e volume of distribution at steady state for CPZ were observed between the treatment groups. Our findings suggest that LPS induces changes i n the pharmacokinetics of CPZ as a result of changes occurring in the biliary secretory system.