Pharmacokinetics of doxorubicin and epirubicin in mice during chlorpromazine-induced hypothermia

• Published in: Cancer chemotherapy and pharmacology Vol. 40; no. 5; pp. 419 - 424
• Main Authors: LUNDGREN-ERIKSSON, L, CARLSSON, A, EKSBORG, S, RYD, W, VESANEN, R, HULTBORN, R
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1997
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacokinetics; Antineoplastic agents; Area Under Curve; Biological and medical sciences; Chlorpromazine; Doxorubicin - pharmacokinetics; Epirubicin - pharmacokinetics; Female; General aspects; Half-Life; Hypothermia - blood; Hypothermia - chemically induced; Male; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Antineoplastic agent; Intraperitoneal administration; Intravenous administration; Body temperature; Rodentia; Phenothiazine derivatives; Chlorpromazine; Doxorubicin; Blood; Vertebrata; Mammalia; Mouse; Animal; Anthracyclins; Combined treatment; Epirubicin; Pharmacokinetics; Hypothermia
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800050680

Blood concentrations of doxo- and epirubicin were studied in mice after i.v. or i.p. administration under normal and hypothermic conditions. The animals either were pretreated i.p. with chlorpromazine at 15 mg/kg and allowed to cool to a rectal temperature of 28 degrees C or were given saline i.p. with their rectal temperature remaining at 37 degrees C. The anthracyclines were 14-14C-labeled and were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min and 2, 6, 24, and 48 hours after injection and were analyzed by liquid scintillation counting. The blood concentration related to time was similar for the two anthracyclines. The peak concentration was highest for i.v. administration and was higher for the hypothermic groups. The peak concentration and the area under the curve were highest under hypothermic conditions. The terminal half-life was longer after i.p. administration. The ratio calculated for the blood concentration under hypothermic/normothermic conditions over time was substantially increased after i.p. administration, the increase being most pronounced for epirubicin. The pharmacokinetic characteristics found might be related to the anthracycline toxicity encountered in tumor-inoculated mice treated at different body temperatures.