A carrier-mediated transport system for benzylpenicillin in isolated hepatocytes.

The transport mechanism of benzylpenicillin was studied in freshly prepared rat hepatocytes. The initial uptake rate followed both saturable and unsaturable transport processes. The Arrhenius plot of the initial uptake rate gave an activation energy of 16.8 kcal mol-1 (69 kJ mol-1). The benzylpenicillin uptake by hepatocytes was significantly inhibited by antimycin A, sodium cyanide, rotenone, 2,4-dinitrophenol, phenoxymethylpenicillin, probenecid and taurocholic acid. No significant inhibition was observed by acetylaminohippuric acid and several kinds of amino acids and dipeptides. The present study provides the first evidence for the existence of a carrier-mediated and energy-dependent transport system of benzylpenicillin in the liver.