Piroxicam—dietary interactions in a long‐term tolerance study in mice

Abstract

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 the mice. This suggests 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.