Evidence for the existence of a common transport system of beta-lactam antibiotics in isolated rat hepatocytes.
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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010400:Penicillin G / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D010400:Penicillin G