Pharmacokinetics of adriamycin and adriamycinol after intravenous administration of adriamycin to rats with water-deprivation for 48 hours.
Because hormonal, physiological, and biochemical changes occurring in dehydrated patients could alter the pharmacokinetics of the drugs used to treat the patients, the pharmacokinetics and tissue distribution of adriamycin (ADM) and adriamycinol were investigated after 1-min intravenous administration of ADM (16 mg kg-1) to control and 48-h water-deprived rats. After intravenous administration of ADM, the plasma levels of ADM were considerably higher from 3 h in water-deprived rats (n = 10) than those in control rats (n = 11). The total body clearance was significantly slower (80.3 compared with 110 mL min-1 kg-1) in water deprived rats than that in control rats. Adriamycinol was detected in plasma up to 30 min for water-deprived rats, but it was detected only up to 5 min for control rats with considerably higher levels in water-deprived rats. The amount of ADM obtained from kidney, liver, spleen, and small intestine was significantly higher in water-deprived rats (n = 6) than those in control rats (n = 5). The amount of adriamycinol obtained from liver was significantly higher in water-deprived rats. All 11 control rats survived over 48 h whereas 5 water-deprived rats died within 8 h after intravenous administration of ADM, suggesting that the intravenous dose of ADM in water-deprived 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.
Lee
M G
MG
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003681:Dehydration / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014868:Water Deprivation
D004317:Doxorubicin; C010013:adriamycinol