Evaluation of the toxicity of indomethacin in a 4-week study, by oral route, in the marmoset (Callithrix jacchus).
A subacute toxicity study of Indomethacin administered by oral route, was carried out in the marmoset (Callithrix jacchus). Groups of three males and three females received Indomethacin directly into the stomach by means of a catheter for a period of 4 weeks at the dose levels of 0, 2, 6, and 12 mg/kg body wt/day and then were euthanized for pathological evaluation. All marmosets given 12 mg/kg/day and one marmoset given 6 mg/kg/day died during the dosing period (within 20 days). At 12 mg/kg/day, Indomethacin induced severe gastrointestinal toxicity (hemorrhage, ulcers, and necrosis with peritonitis), while at the dosages of 6 and 2 mg/kg/day some moderate to slight dose-related functional and morphological renal alterations (increase of serum urea, reduction of serum albumin, increase of serum potassium and/or chloride, and subacute inflammation) were observed. The fact that in many respects these alterations are similar to those observed in man is a further demonstration of the validity of the marmoset as an experimental model.
Oberto
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Istituto di Richerche Biomediche, Antoine Marxer, RBM-Ivrea (TO), Italy.
Conz
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A
Giachetti
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Galli
C L
CL
D000284:Administration, Oral; D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002144:Callithrix; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology; D007213:Indomethacin / Q000097:blood / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects
D007213:Indomethacin