Evaluation of antitumor and toxic side effects of mitomycin C-estradiol conjugates.
The antitumor and toxic side effects of mitomycin C-estradiol conjugates (EB-glu-MMC and E-glu-MMC) were evaluated in detail for solutions in propylene glycol and suspensions in 10% (v/v) propylene glycol. Tumor growth, body weight and number of leukocytes were examined after i.p. administration to sarcoma 180 solid tumor-bearing mice. Body weight and number of leukocytes were also examined in normal mice after i.p. administration of the solution. In solution dosage forms, the two conjugates had almost the same suppressive effect on tumor growth at 30 mg MMC eq./kg as MMC at 5 mg/kg, did not lower body weight significantly, but reduced the number of leukocytes at 30 mg MMC eq./kg. MMC, lethally toxic at 10 mg, significantly lowered the body weight and leukocyte number. In the suspension dosage forms, these conjugates had a greater suppressive effect on tumor growth at 50 mg MMC eq./kg than MMC at 5 mg/kg, and reduced the body weight and leukocyte number, with E-glu-MMC more toxic than EB-glu-MMC. The presence of the tumor itself influenced the body weight and leukocyte number. However, toxic side effects could be evaluated from the body weight and leukocyte number to almost the same extent between tumor-bearing and normal mice.
Ishiki
Nobuyuki
N
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
Onishi
Hiraku
H
Machida
Yoshiharu
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D016685:Mitomycin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000473:pathology*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D004958:Estradiol; D016685:Mitomycin