Fourteen-day oral combination dose toxicity study of CGS 16949 A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats.
CGS 16949A, an aromatase inhibitor, was administered orally to female rats at doses of 1 and 10 mg/kg/day alone and in combination with tamoxifen (0.5 or 5 mg/kg/day) or 5-fluorouracil (20 mg/kg/day) for 14 days. CGS 16949A and tamoxifen combination: Increased food intake and body weight noted after CGS 16949A treatment were also observed following combination treatment, though to a lesser degree. Most of the clinical pathological features noted following combination treatment were similar to those induced by single compound treatment. Gross pathological and histopathological changes ascribed to the antiestrogenic action of CGS 16949A, such as increased ovarian weight, decreased uterine weight, cystic follicles and atrophied uterus and vaginal epithelium, were alleviated by combination treatment, and were comparable in severity to those caused by tamoxifen alone. No severe toxic changes were induced by combination treatment. CGS 16949A and 5-fluorouracil combination: Increased body weight noted after CGS 16949A treatment was also observed following combination treatment, though to a lesser degree. Most of the changes caused by single compound treatment, including the aforementioned effects of CGS 16949A on the genital organs, were also noted following combination treatment. There was no evidence of enhancement of the effects by combination treatment.
Matsuda
A
A
Ina Research Inc, Nagano-ken, Japan.
Higuchi
K
K
Karasawa
M
M
Yoneyama
S
S
Deguchi
J
J
Miyamoto
M
M
D000284:Administration, Oral; D000818:Animals; D047072:Aromatase Inhibitors; D001772:Blood Cell Count / Q000187:drug effects; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D017316:Fadrozole / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000008:administration & dosage / Q000633:toxicity*; D016482:Urinalysis; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014621:Vagina / Q000187:drug effects / Q000473:pathology
D047072:Aromatase Inhibitors; D013629:Tamoxifen; D017316:Fadrozole; D005472:Fluorouracil