Effect of high dose alpha-tocopherol acetate on the toxicity and tissue distribution of adriamycin (doxorubicin).
The effect of alpha-tocopherol acetate (VE) on the toxicity and tissue distribution of adriamycin (ADM) in mice was studied. After the administration of ADM in 2 doses of 15 mg/kg, mice pretreated with olive oil survived 7.1 +/- 1.0 days, while mice pretreated with VE in ten doses of 500 mg/kg/day (subcutaneously) survived 5.5 +/- 1.7 days (p less than 0.01). The total concentration of ADM and its major metabolite, aglycone I in the liver (1, 3, 5 h), kidneys (1, 3 h), and heart (3 h), as determined by high performance liquid chromatography was significantly higher in the VE-pretreated group (four doses of 500 mg/kg/day) than in the olive oil-pretreated group. The aglycone levels of the VE-pretreated group were significantly higher than those of the olive oil-pretreated group in the liver, kidney and heart, but there was no significant difference between the groups in the levels of the unmetabolized form. Considering these results, the administration of VE concomitant with anti-tumor drugs, including ADM, requires great caution.
Shinozawa
S
S
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Gomita
Y
Y
Araki
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism*; D014018:Tissue Distribution; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D014810:Vitamin E; D004317:Doxorubicin; D024502:alpha-Tocopherol; D024505:Tocopherols