title: 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.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom; Centre for Pharmaceutical Studies, Laboratory of Pharmaceutical Science, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Chymiotechnon and Department of Chemistry, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Amélia C F
authors.initials: AC
authors.lastname: Vieira
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom. Electronic address: s.murdan@ucl.ac.uk.
authors.forename: Sudaxshina
authors.initials: S
authors.lastname: Murdan
authors.affiliation: Chymiotechnon and Department of Chemistry, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Arménio C
authors.initials: AC
authors.lastname: Serra
authors.affiliation: Centre for Pharmaceutical Studies, Laboratory of Pharmaceutical Science, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Veiga
authors.affiliation: Chymiotechnon and Department of Chemistry, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: António M d'A Rocha
authors.initials: AM
authors.lastname: Gonsalves
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom. Electronic address: a.basit@ucl.ac.uk.
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Basit
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004008:Diclofenac / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004032:Diet; D004355:Drug Stability; D005215:Fasting; D065569:Gastrointestinal Absorption; D005772:Gastrointestinal Transit; D006863:Hydrogen-Ion Concentration; D008297:Male; D011355:Prodrugs / Q000378:metabolism / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000378:metabolism / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D011355:Prodrugs; D047392:beta-Cyclodextrins; D004008:Diclofenac; D012460:Sulfasalazine; C031215:betadex
keywords: Colonic targeting; Fasting; Feeding; Gastro-intestinal transit; Prodrug degradation; Regimen