Studies of the kinetics of purified conjugated bilirubin-3H in the rat

Abstract

Radio-labeled conjugated bilirubin was purified from rat bile by affinity chromatography. Following the intravenous injection of tracer doses of this material, the initial fractional plasma disappearance rate of conjugated bilirubin-3H in the normal Sprague-Dawley rat was found to be approximately 50% faster than that for unconjugated bilirubin-3H (0.51 +/- 0.94 [SE] vs. 0.35 +/- 0.02 min.-1; P less than .001). Hepatic recovery studies in the rat indicated that, over the first four minutes after injection, disappearance of cholephilic anions from plasma is accounted for almost entirely by hepatic uptake. Hence, these studies demonstrate that hepatic uptake of conjugated bilirubin is substantially faster than that of unconjugated bilirubin. Net hepatic clearance of conjugated bilirubin in normal rats was three-fold greater than that of unconjugated bilirubin (0.94 +/- 0.16 vs. 0.30 +/- 0.03 ml./min./100 gm. body weight; P less than .001), presumably reflecting both the more rapid hepatic uptake and the ability of the former pigment to by-pass the conjugation step. Hepatic uptake of conjugated bilirubin was shown to be inhibited by unconjugated bilirubin, sulfobromophthalein and indocyanine green but not by glycocholate. These observations cannot be explained by simple diffusion and suggest that the hepatic uptake mechanism for conjugated bilirubin is the same as that for the unconjugated pigment.