Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-β-cyclodextrin

Abstract

Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated.

The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac-β-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity.