Localisation of drug permeability along the rat small intestine, using markers of the paracellular, transcellular and some transporter routes.
The small intestine is the major site of drug absorption. Some reports in the literature have evoked the concept of "absorption windows" in the small intestine: are there specific regions where drug absorption is significantly higher than others? To investigate this question, we used an everted gut sac method to study the permeability of drugs and markers every 3-4cm down the entire small intestine in rat. These markers were chosen to be representative of the mechanisms by which drugs cross the small intestinal mucosa: paracellular and transcellular passive diffusion, via influx transporters, and a drug (digoxin) that is effluxed from cells by P-glycoprotein (P-gp). The passive diffusion and influx transporter markers gave similar profiles with a plateau of permeability along the jejunum, and with the exception of L-Dopa, lower permeability in the ileum. Digoxin showed a linear decrease in the profile from the proximal jejunum to the ileum. Permeability in the duodenum was two to three times lower than the jejunum for all compounds. There were no narrow specific regions of high permeability and so the concept of discrete "absorption windows" along the small intestine as suggested from some pharmacokinetic studies may be related to other effects such as pH and/or solubility.
Lacombe
Olivier
O
Laboratoire de Cinétique des Xénobiotiques, UMR 181 Physiopathologie et Toxicologie Expérimentale (UPTE INRA-ENVT), Faculté des Sciences Pharmaceutiques, 35 chemin des Maraîchers, 31062 Toulouse Cedex, France.
Woodley
John
J
Solleux
Claude
C
Delbos
Jean-Marie
JM
Boursier-Neyret
Claire
C
Houin
Georges
G
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D002463:Cell Membrane Permeability; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D013194:Staining and Labeling / Q000379:methods
D015415:Biomarkers; D004364:Pharmaceutical Preparations