PRILOCAINE ELIMINATION BY ISOLATED-PERFUSED RAT LUNG AND LIVER

Prilocaine is assumed to undergo significant elimination by extrahepat ic organs and to differ in this respect from other commonly used local anaesthetics. In order to clarify whether the lung may play an import ant role as a site of elimination of prilocaine, the kinetic parameter s were studied in isolated perfused rat lungs and were compared to tho se of isolated livers. Furthermore, the structurally related compounds bupivacaine and mepivacaine were also investigated in this system. Pr ilocaine was dispersed into a relatively large apparent distribution v olume in perfused rat lung (139 ml versus 97 ml in controls). In singl e-pass perfused lungs the observed maximum of concentration was decrea sed by about 60% compared to controls. The mean residence time was pro longed by about 40%. These observations suggest that prilocaine is sub stantially retained by rat lung and that this effect occurs particular ly during first-pass. However, the ability of rat lung to degrade pril ocaine was relatively low. The clearance values were about 0.3 ml/min equal to about 20% of the hepatic capacity calculated per g of tissue. Thus it must be assumed that prilocaine is only transiently retained by the lung and will gain systemic availability later on. In rat lungs the kinetics of prilocaine elimination were not substantially differe nt from those of bupivacaine and mepivacaine (16 and 12%), These obser vations do not support the assumption that especially prilocaine under goes extrahepatic elimination. For low (2 mu g/ml) and intermediate (1 0 mu g/ml) drug concentrations isolated rat liver exhibited clearance values close to the perfusion flow rate. Accordingly, prilocaine was r emoved from the perfusion medium of isolated livers already during fir st-pass. At very high concentrations of 100 mu g/ml, the clearance dro pped to about half of the control values. Thus under these conditions approximately half of the dose escaped first-pass extraction which is probably caused by saturated metabolic clearance. Such an effect was n ot observed for bupivacaine and mepivacaine.