Hepatobiliary Excretion of Dipyrrinone Sulfonates in Mrp2-Deficient (TR −) Rats

The biliary excretion of the sodium salts of 8-(2-ethanesulfonic acid)-3-ethyl-2,7,9-trimethyl-1,10-dihydro-11 H-dipyrrin-1-one (xanthosulfonic acid) and a fluorescent analogue (8-desethyl- N, N′-carbonyl-kryptopyrromethenone-8-sulfonic acid) was compared in Mrp2-deficient (TR −) and normal rats. Both organic anions were excreted rapidly in bile in Mrp2-deficient rats, but the biliary excretion of the fluorescent sulfonate was impaired relative to normal controls. The rat clearly has efficient Mrp2-independent mechanisms for biliary efflux of these anions that are not used by bilirubin or its mono- and diglucuronides. Sulfonate 5 and the highly fluorescent analogue, 7, were excreted rapidly in bile in rats following iv administration. Biliary excretion of 5 was not markedly impaired in Mrp2-deficient (TR −) rats, but that of 7 was reduced. Both of these dipyrrinone organic anions can be cleared from blood and excreted rapidly in bile by Mrp2-independent mechanisms in the rat.