Bile secretory function: a determinant of adriamycin disposition.
Adriamycin (ADR) is rapidly cleared from plasma and enters tissues, while it is extensively eliminated in bile and moderately in urine following i.v. injection of 20 mg/kg to anesthetized rats. In bile duct- and bladder-cannulated rats with physiologic bile and urine production, 26.6% of the injected ADR is excreted in bile as total ADR equivalents during a 3 hr period and 4.4% in urine. When the elimination of the drug in urine is prevented by ligation of the kidneys, no significant differences are observed in the disposition of the total drug equivalents. Conversely, when bile flow is inhibited by the administration of sodium taurolithocholate, the biliary excretion of the total ADR equivalents declines significantly and in a fashion related to the degree of bile flow reduction. In parallel with the diminished biliary elimination, the urinary excretion increases significantly and is responsible for most of the drug eliminated when severe cholestasis is produced. However, despite the increased urinary excretion, the overall elimination of the total ADR equivalents in cholestatic rats is significantly reduced and both plasma and tissue levels of the total drug equivalents rise significantly and in a fashion closely related to the degree of the induced cholestasis.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000502:physiology; D002779:Cholestasis / Q000378:metabolism; D004317:Doxorubicin / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000502:physiology
D004317:Doxorubicin