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The inhibition effect of several beta-lactam antibiotics on the uptake of [14C]benzylpenicillin (PCG) into isolated rat hepatocytes was studied. Monobasic beta-lactam antibiotics such as apalcillin, cloxacillin, nafcillin, piperacillin, cefmetazole, cefoperazone, cefpiramide and cephalothin significantly inhibited the uptake of PCG, while amphoteric beta-lactam antibiotics such as amoxicillin, ciclacillin, cephradine, cephalexin and cephaloridine had a slight inhibitory effect on the uptake of PCG. Five monobasic compounds of these antibiotics used (apalcillin, nafcillin, piperacillin, cefmetazole and cefoperazone) which have a tendency to be excreted into bile to a large extent, inhibited the initial uptake rate of PCG in a fully competitive fashion according to the Lineweaver-Burk plots and the corresponding modified Inui-Christensen plots. Thus, it was concluded that almost all beta-lactam antibiotics have a common carrier system responsible for their uptake into isolated rat hepatocytes, but it is still uncertain whether or not amphoteric beta-lactam antibiotics have another specific transport system.

Evidence for the existence of a common transport system of .BETA.-lactam antibiotics in isolated rat hepatocytes.