A Study of the Mechanism of Biliary Excretion of Several Dyes Extensively Excreted in Bile

Abstract

1. The submaximal biliary excretion of four unmetabolised dyes which are extensively excreted in the bile of rats was studied. The dyes used were bromocresol green, amaranth, indocyanine green and phenol-3, 6-dibromophthalein [35S] disulphonate. Each dye was administered as a single intravenous dose to bile-duct-cannulated rats. 2. Biliary excretion data from animals of uncontrolled body temperatures or of known different rectal temperatures were plotted using six plotting methods. The biliary excretion of bromocresol green, amaranth and phenol-3, 6-dibromophthalein [35S] disulphonate appeared to depend on the volume of bile excreted rather than on time. The excretion of bromocresol green in rats of rectal temperature 37°c also appeared to be dependent on bile volume rather than on time. Indocyanine green excretion in rats of uncontrolled body temperature showed a degree of variation too large to be accounted for by differences in bile flow alone. 3. Taurocholate choleresis did not promote submaximal biliary excretion of amaranth at the infusion levels of taurocholatd and dose level of amaranth used. 4. Twenty minute obstruction of bile flow prior to dosing had little effect on bromocresol green biliary excretion. 5. Unanaesthetised rats showed poorer bromocresol green excretion than did anaesthetised rats. 6. Hepatic levels of bromocresol green and phenol-3, 6-dibromophthalein [35s] disulphonate showed apparent dependence on bile volume excreted after dosing, rather than on time. Similarly, the relationships between the hepatic levels and the biliary excretion of both dyes were consistent with bile volume dependence of their excretion. 7. Two models of bile volume dependent liver-to-bile dye transport were considered. 8. The implications of bile volume dependent excretion, for in vivo kinetic studies of compounds extensively in the bile, were discussed.