Enhanced intestinal motility influences absorption in anaesthetized rat.
The subject of this investigation was to study influence of the intestinal motility on absorption of 3-o-methyl-D-glucose (3-OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin(R) and Rapinovet(R). A segment of duodenum, approximately 10 cm, was perfused single-pass with saline containing unlabelled and radioactive 3-OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet, which showed a 'burst-type' pattern resembling migrating motor complex (MMC). Absorption of 3-OMG in rats with MMC-like motility appears to be lower than in rats with fed-like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r 2=0.75) between intestinal activity (fed) and absorption of 3-OMG, but not with absorption of mannitol. The carrier-mediated absorption of 3-OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.
Sababi
M
M
Department of Discovery DMPK, AstraZeneca, Lund, Sweden. manaf.sababi@astrazeneca.com
Bengtsson
U H
UH
D019325:3-O-Methylglucose / Q000378:metabolism; D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004338:Drug Combinations; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008723:Methohexital / Q000494:pharmacology; D023421:Models, Animal; D011092:Polyethylene Glycols / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013874:Thiopental / Q000031:analogs & derivatives / Q000494:pharmacology*
D000777:Anesthetics; D004338:Drug Combinations; D019325:3-O-Methylglucose; C004316:thiobutabarbital; D008353:Mannitol; D011092:Polyethylene Glycols; D008723:Methohexital; D013874:Thiopental; D015742:Propofol