Membrane permeability and antipyrine absorption in a rat model of ischemic colitis.
The aim of this study was to determine whether the duration of ischemia affects antipyrine absorption in the large intestine. This was carried out in a rat model of ischemic colitis in which ischemia and associated inflammation was induced by marginal vessel ligation. Blood flow was disrupted by positioning an o-ring around the distal rectum and ligating the marginal vessel at two locations in the hind-gut ligament artery region. Ligation was performed for 1, 2, 3, and 5h. We assessed large intestine damage by measuring key indicators of inflammation, myeloperoxidase (MPO) activity and thiobarbituric acid reactant substrates (TBARS) in the mucosa and by histological staining with hematoxylin-eosin stain. Antipyrine membrane permeability was assessed in Ussing-type diffusion chambers, and related pharmacokinetics were calculated from antipyrine plasma concentration measurements following colon administration of the drug. Vessel ligation caused some sloughing of epithelial cells and elevated the MPO and TBARS levels. Prolonged ligation failed to affect the apparent permeability coefficient (P(app)) of antipyrine. Prolonged ligation, however, gradually increased plasma antipyrine concentrations to near control levels. This increase was paralleled by increases in the absorption rate constant AUC and antipyrine bioavailability. Taken together, these results suggest that the absorption kinetics of antipyrine may depend on blood flow changes in the large intestine that occur with inflammation.
Koga
Kenjiro
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan. k-koga@hokuriku-u.ac.jp
Ishitobi
Yoshiro
Y
Kawashima
Susumu
S
Taniguchi
Masakazu
M
Murakami
Masahiro
M
D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D017091:Colitis, Ischemic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D044683:Colon, Descending / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007564:Japan; D008026:Ligation / Q000379:methods; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D009195:Peroxidase; D000983:Antipyrine