Toxicological aspects of feprazone,a new nonsteroidal anti-inflammatory drug |
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Authors: | Tamotsu Koyama Yoshihiro Izawa Hiroshi Wada Tokutaro Makita Yoshinobu Hashimoto Makoto Enomoto |
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Institution: | Teijin Institute for Biomedical Research, Asahigaoka 4-3-2, Hino, Tokyo 191, Japan |
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Abstract: | The subacute and chronic toxicities of oral feprazone were studied in rats and beagle dogs. Administration of more than 150 mg/kg/day of feprazone to rats for 1 month induced retardation of growth and liver enlargement. In addition, treatment with 600 mg/kg/day of feprazone caused death, gastrointestinal ulcers, decreased hemoglobin concentration, and leucocytosis. Treatment of rats with 540 mg/kg/day of feprazone for 6 months had similar effects to those described above except that it did not cause death or gastrointestinal ulcers. Toxic nephropathy, nontoxic goiter, hepatomegaly, and increase of ovarian weight were observed in rats given more than 60 or 180 mg/kg/day of feprazone for 6 months. Injection of 1080 mg/kg/day of feprazone into dogs, caused one of six animals to become moribund on Day 18 and one to die on Day 7. The dogs surviving after administration of 360 and 1080 mg/kg/day of feprazone for 1 month showed anemia, leucocytosis, and elevations of phenolsulfonphthalein retention and serum alkaline phosphatase (ALP) activity. Similar effects were observed in dogs surviving after treatment with 150 or 375 mg/kg/day of feprazone for 12 months; in addition, increased ALP activity was observed even at a dose of 60 mg/kg/day. Liver enlargement was observed in dogs treated with all doses of feprazone for 1 or 12 months, and cytoplasmic inclusion bodies were observed in liver cells of dogs given more than 120 mg/kg/day of feprazone for 1 month. |
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