Piroxicam--dietary interactions in a long-term tolerance study in mice.
Piroxicam is a commonly prescribed nonsteroidal anti-inflammatory drug. In this study, piroxicam was fed at 60 ppm to mice in a semipurified AIN-76A (low-fat) control diet and in a Western-style diet (i.e., a modified AIN-76A diet with increased fat and reduced calcium and vitamin D, developed as a mimic of the human "Western" diet in the United States). Piroxicam in the AIN-76A diet produced only small adverse effects. However, 21-28 weeks of feeding piroxicam in the Western-style diet was lethal to mice. This suggest potent magnification of piroxicam toxicity in a high-fat-containing Western-style diet. This surprising finding suggests careful consideration of diet composition when potent agents such as nonsteroidal anti-inflammatory drugs are tested in animal studies and in clinical trials by humans who ingest the high-fat diets of Western countries.
Strang Cancer Prevention Center, New York, NY 10021, USA.
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Croll-Halpern
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Newmark
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Monaghan
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M
Lipkin
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004361:Drug Tolerance; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010894:Piroxicam / Q000008:administration & dosage / Q000633:toxicity*; D015996:Survival Rate; D015430:Weight Gain
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004041:Dietary Fats; D010894:Piroxicam