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

Abstract

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.

Species differences in the developmental toxicity of procymidone

“…The radiation dose was set at about 3.70 MBq/kg. For the pharmacokinetic studies, blood was collected from the caudal vein (rats), an auricular vein (rabbits), a femoral vein (monkeys), or the abdominal aorta (at 120 hr only for rats and rabbits) 1, 2, 4, 6 (rats only), 8,10,12,24,48,72, and 120 hr after administration. For the excretion studies, after administration, animals were housed individually in metabolic cages to allow separate collection of urine and feces.…”

Biliary excretion of some diquaternary ammonium cations in the rat, guinea pig and rabbit

“…4. These results together with data from the literature suggest that the molecular weight at which the excretion of dications in the bile exceeds 10% of the dose is in the region of 500-600, which differs from the values for monocations (Hughes et al, 1973) and anions (Millburn et al, 1967;Hirom et al, 1972).…”

“…4. These results together with data from the literature suggest that the molecular weight at which the excretion of dications in the bile exceeds 10% of the dose is in the region of 500-600, which differs from the values for monocations (Hughes et al, 1973) and anions (Millburn et al, 1967;Hirom et al, 1972).From a study of the biliary excretion in the rat, guinea pig and rabbit of some monoquaternary ammonium or pyridinium cations, Hughes et al (1973) suggested that there is a molecular-weight threshold of about 200±50 for the significant (i.e. 10% or more of the dose) biliary excretion of monoquaternary nitrogen cations in these species.…”

“…It is ofinterest that the structure of d-tubocurarine has been questioned, and Everett et al (1970) and Codding & James (1972) Hughes et al (1973) have suggested that for the biliary excretion of monoquaternary nitrogen cations in amounts greater than 10% of the dose, the cation should have a molecular weight of not less than about 200±50. For anions this minimum molecular weight was for the rat about 325±50 (Millburn et al, 1967;Hirom et al, 1972). The data for diquaternary nitrogen cations are less extensive than for the monocations and anions, but are sufficient to make the tentative suggestion that this minimum molecular weight for dications is different from that for monocations and anions and is probably in the region of 500-600.…”

Metabolic fates of diethylstilboestrol sulphates in the rat

“…Rats (three male and three female) with bile-duct and ureter cannulae received intravenous injections of potassium diethylstilboestrol mono [35S] At relatively high dosages there was no significant biliary elimination of either mono-or di-sulphate esters of diethylstilboestrol, although diethylstilboestrol disulphate does fulfil the requirements of molecular weight, anionic character and lipophilic nature suggested (Hirom et al, 1972) as necessary for biliary elimination. Either there is no mechanism for the biliary elimination of these esters or the metabolism is so rapid that no biliary elimination of the compound is observed.…”