Effects of Administration of Hydrocortisone on the Renal and Biliary Excretion of Ampicillin in the Dog

Abstract

Hydrocortisone produced choleresis in anesthetized dogs receiving taurocholate and ampicillin. There was an increase in mean concentration of ampicillin in serum after infusion of hydrocortisone with no change in mean rate of biliary excretion of ampicillin. In dogs receiving creatinine in addition to taurocholate and ampicillin, hydrocortisone also produced an increase in mean levels of ampicillin in serum. The mean rate of biliary excretion and the rate of renal clearance of ampicillin were constant in these dogs. In dogs receiving creatinine, taurocholate, and ampicillin without infusion of hydrocortisone, mean concentration of ampicillin in serum, minute biliary weight, and renal clearance rate of ampicillin remained constant throughout the 150 min of study, while mean biliary concentration of ampicillin and rate of excretion decreased during the last 40 min. The increased concentrations of ampicillin in serum of dogs during and after infusion of hydrocortisone seems due to decreased diffusion of ampicillin from plasma into the hepatocyte. Preliminary chromatographic studies of rat liver supernate on Sephadex G-75 indicate that bioactivity of ampicillin appears at a position in the elution pattern where Y protein should be eluted. Y protein binds anoinic metabolites of cortisol. Competitive or noncompetitive inhibition by hydrocortisone of binding of ampicillin to Y protein could explain the increased concentrations in serum during and after infusion of hydrocortisone.