EFFECTS OF CHOLESTYRAMINE AND PARENTERAL-NUTRITION ON HEPATIC-METABOLISM OF LIDOCAINE - A STUDY USING ISOLATED RAT-LIVER PERFUSION

Background: The effect of an oral bile salt binder, cholestyramine, on parenteral nutrition-related hepatic dysfunction and Lidocaine metabo lism was studied in rats. Methods: Rats were randomly assigned to one of three treatment groups: the PN group received infusions of dextrose and amino acids; the PNC group was treated the same as the PN group, but also received oral cholestyramine; CF group animals were fed rat f ood and water. Lidocaine metabolism was studied in Livers isolated fro m animals after 7 days of parenteral nutrition. Results: No difference s in Liver function test values of PN and PNC groups were detected com pared with group fed rat food. However, lidocaine metabolism was found to be significantly reduced in both the PN and PNC groups. Significan t reductions were observed in the hepatic extraction ratio (23% and 15 %) and in intrinsic clearance (61% and 53%) in PN and PNC animals, res pectively (P<.05). Material balance at steady state showed that recove ry of Lidocaine was threefold higher in the PN group and twofold highe r in the PNC group than the rat food group (P < .05). Metabolite-to-dr ug ratios were determined for each lidocaine metabolite and this revea led significant reductions in N-dealkylation (64% and 57%) and aryl me thyl hydroxylation (92% and 86% in PN and PNC animals, respectively (p <.05). Conclusions: Histologic findings sug gest that cholestyramine f eeding prevented liver dysfunction, possibly through interruption of s econdary bile salt reabsorption. However, lidocaine metabolism was sti ll impaired after cholestyramine ingestion; the impairment mechanism r emains unknown.