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.