ALPHA-INTERFERON HAS NO EFFECT ON LIDOCAINE METABOLISM IN THE RAT

Interferons (IFN) inhibit activity of many isoenzymes of the hepatic m icrosomal cytochrome P-450 system. This inhibition is species specific . Lidocaine is metabolized by cytochrome P-450 III A 4. We investigate d in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine eli mination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blo od was drawn from the arterial catheter for lidocaine determination ev ery 3 min for 20 min. 7 rats were pre-treated with intramuscular rat a lpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rat s were given saline i.m. The lidocaine elimination rate constant was u nchanged, 0.065 min(-1) and 0.063 min(-1) for the control and IFN grou ps, respectively. To investigate lidocaine extraction, the isolated pe rfused rat liver was used. Perfusate samples from the portal and hepat ic veins were drawn at 2 min intervals for 20 min, and lidocaine extra ction determined. Extraction was determined in two groups of 6 rats ea ch. The first-group served as control and these rats were injected wit h saline only, while in the second group, the rats were pre-treated wi th rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated p erfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded t hat the rat alpha-IFN affects neither the elimination nor the extracti on of lidocaine.