Pharmacokinetic and tissue distribution changes of adriamycin and adriamycinol after intravenous administration of adriamycin to uranyl nitrate-induced acute renal failure rats.
The pharmacokinetic and tissue distribution changes of adriamycin (ADM) and adriamycinol were investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the control and the uranyl nitrate-induced acute renal failure (U-ARF) rats. After 1 min i.v. infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2 to 12 hr in the U-ARF rats, whereas the levels were detected for only up to 3 hr in the control rats. Adriamycinol was detected in plasma for up to 180 min for the U-ARF rats, but, it was detected for only up to 1 min for the control rats with significantly higher levels in the U-ARF rats. The mean amount of both ADM and adriamycinol excreted in urine were significantly smaller in the U-ARF rats than those in the control rats due to the decreased kidney function in the U-ARF rats. In tissue distribution studies, the amount of ADM obtained from the heart, liver, spleen, small intestine, large intestine, and fat were significantly higher in the U-ARF rats than those in the control rats. The tissue to plasma ratios of the liver, spleen, large intestine, and fat also increased significantly in the U-ARF rats than those in the control rats. The amount of adriamycinol obtained from the heart, spleen, and liver were significantly higher in the U-ARF rats. All 7 control rats survived over 48 hr whereas 6 out of 8 U-ARF rats died between 36-48 hr after i.v. administration of ADM, suggesting that the i.v. doses of ADM in acute renal failure patients may need modification if the present rat data could be extrapolated to humans.
Lee
H J
HJ
College of Pharmacy, Seoul National University, Korea.
Paik
W H
WH
Lee
M G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014502:Uranyl Nitrate
D000903:Antibiotics, Antineoplastic; D014502:Uranyl Nitrate; D004317:Doxorubicin; C010013:adriamycinol