Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions.

1. The excretion in the bile and urine after intravenous injection of 16 organic anions having molecular weights between 355 and 752 was studied in female rats, guinea pigs and rabbits. 2. These compounds were mostly excreted unchanged, except for three of them, which were metabolized to a slight extent (<7% of dose). 3. The rat excreted all the compounds extensively (22-90% of dose) in the bile. 4. In guinea pigs four of the compounds with mol.wt. 355-403 were excreted in the bile to the extent of 7-16% of the dose, four with mol.wt. 407-465 to the extent of 25-44% and eight compounds with mol.wt. 479-752 to the extent of 44-100%. 5. In rabbits four compounds with mol.wt. 355-465 were excreted in the bile to the extent of 1-8% of the dose, two compounds with mol.wt. 479 and 495 to the extent of 24 and 22%, and six compounds with mol.wt. 505-752 to the extent of 31-94%. 6. These results, together with those of other investigations from this laboratory, are discussed and the conclusion is reached that there is a threshold molecular weight for appreciable biliary excretion (i.e. more than 10% of dose) of anions, which varies with species: about 325+/-50 for the rat, 400+/-50 for the guinea pig and 475+/-50 for the rabbit. 7. Anions with molecular weights greater than about 500 are extensively excreted in the bile of all three species. 8. That proportion of the dose of these compounds which is not excreted in the bile is excreted in the urine, and in the three species, bile and urine are complementary excretory pathways, urinary excretion being greatest for the compounds of lowest molecular weight and tending to decrease with increasing molecular weight. 9. Some implications of this interspecies variation in the molecular-weight requirement for extensive biliary excretion are discussed.