Effect of biliary stasis and hepatotoxins on the excretion of iopanoate in the rat.
In rats, hepatic dysfunction was induced with CCl4, SKF 525-A, taurolithocholic acid and alpha-naphthylisothiocyanate and by acute and chronic surgical ligation of the bile duct. Biliary and urinary excretion of 125I-labeled iopanoate was measured after a standard i.v. dose. In the absence of normal biliary excretion, the amount excreted in the urine varied over a wide range (0.25-11.2 percent of the dose), with highest rates of urinary excretion occurring after alpha-naphthylisothiocyanate and chronic stasis. Drug disposition was further determined by tissue analysis of liver and kidney. The results indicate that, for a drug that is normally almost exclusively excreted by the bile, in the presence of hepatic dysfunction the amount excreted by the alternate urinary route depends on the type of the induced hepatic disorder. The intrarenal distribution of 125I-radioactivity is strongly influenced by its plasma concentration rather than just by the rate of excretion in the urine.
D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000503:physiopathology; D002779:Cholestasis / Q000378:metabolism* / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D005965:Glucuronates / Q000378:metabolism; D007457:Iodine Radioisotopes; D007480:Iopanoic Acid / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008095:Lithocholic Acid / Q000031:analogs & derivatives / Q000506:poisoning; D008099:Liver / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000506:poisoning; D011335:Proadifen / Q000506:poisoning; D051381:Rats; D013656:Taurocholic Acid / Q000031:analogs & derivatives / Q000506:poisoning; D013861:Thiocyanates / Q000506:poisoning
D005965:Glucuronates; D007457:Iodine Radioisotopes; D009281:Naphthalenes; D013861:Thiocyanates; D013656:Taurocholic Acid; D008095:Lithocholic Acid; D011335:Proadifen; D007480:Iopanoic Acid