title: Absorption and metabolism of albendazole after intestinal ischemia/reperfusion.
abstract: Pathophysiological processes involving inflammatory response may affect absorption and biotransformation of some drugs, modifying their pharmacokinetic behaviour. Ischemia/reperfusion (I/R) injury has been used as a model for inflammatory processes. The aim of this work was to study the effect of intestinal I/R injury on the absorption and metabolism processes of one orally administered drug, albendazole that is anthelmintic drug, it undergoes intestinal bioconversion into albendazole sulfoxide by two enzymatic systems, cytochromes P450 (CYP450) and flavin-containing monooxygenase (FMO). Male Wistar rats were used to study the influence of I/R in the intestinal absorption and metabolism of albendazole, after 60 min of mesenteric occlusion and 30 min of reperfusion. The intestinal studies were performed in microsomal, and everted ring incubations. During in situ studies, the I/R group had faster disappearance of albendazole from the lumen. In addition, albendazole only appeared in blood samples of the I/R group, while albendazole sulfoxide appeared in both samples and was higher in the control group. These findings are supported by significant reductions of albendazole sulfoxide formation in intestinal everted ring assays and in microsomal incubations after the I/R process. Both metabolizing systems, CYP4503A and FMO, were affected by I/R. Our data indicate that I/R injury, considered as an inflammatory model, reduces absorption and metabolism processes of albendazole.
authors.affiliation: Department of Physiology, Faculty of Veterinary Medicine, University of Leon, Campus de Vegazana, 24071 Leon, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Molina
authors.forename: Gracia
authors.initials: G
authors.lastname: Merino
authors.forename: Julio G
authors.initials: JG
authors.lastname: Prieto
authors.forename: Rebeca
authors.initials: R
authors.lastname: Real
authors.forename: Gracia
authors.initials: G
authors.lastname: Mendoza
authors.forename: Ana I
authors.initials: AI
authors.lastname: Alvarez
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D007082:Ileum / Q000201:enzymology / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010105:Oxygenases / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D050257:Tubulin Modulators / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000871:Anthelmintics; D050257:Tubulin Modulators; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D051544:Cytochrome P-450 CYP3A; D015766:Albendazole; C027186:albendazole sulfoxide