Biliary and urinary excretion of adriamycin in anesthetized rats.
Adriamycin (ADR), an antibiotic widely used in cancer chemotherapy, is rapidly cleared from plasma, extensively excreted in bile and only moderately in urine during the first few hours after its intravenous injection to anesthetized rats. When bile and urine are collected in bile duct- and bladder-cannulated rats, about 33-35% of the injected doses, 5, 20 or 40 mg/kg ADR, is excreted in bile as total drug equivalents during a 10-hour collection period, while 4-8% is eliminated in urine. Within 60 min from the injection, as much as 15-17% of the dose is excreted in bile and 1-3% in urine. The biliary excretion of ADR, within the dose range of 5-40 mg/kg, is not saturable, is linearly related to the dose administered, and occurs in absence of choleretic or cholestatic manifestations. Conversely, the urinary excretion of the drug is a dose-limited process; when ADR is injected at 40 mg/kg, a significantly lower percentage is eliminated in urine. This decline is associated with a severe, although transient, antidiuretic effect thus suggesting an intrinsic toxicity of the drug at this high dose on renal function.
D000758:Anesthesia; D000818:Animals; D001646:Bile / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D007668:Kidney / Q000601:surgery; D007674:Kidney Diseases / Q000139:chemically induced; D007700:Kinetics; D008026:Ligation; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D013997:Time Factors
D004317:Doxorubicin