[Drug metabolism in the small intestine--the significance for biological availability].
The gut contains drug metabolizing enzymes and drug export proteins, of which the most important are CYP3A4 and P-glycoprotein. P-glycoprotein is localised to the apical membrane and CYP3A4 in the subapical cytoplasmic membranes in the enterocytes. The substrate and modulator specificity overlap between the two systems. The function of the two systems may be integrated. The intestinal first pass effect is the fraction of a drug which is metabolised or excreted during the absorption from the lumen. The significance of the intestinal first pass effect for the bioavailability of the three model drugs, midazolam, cyclosporin and digoxin, has been reviewed. The impact of different disease states in the gastrointestinal tract on the function of intestinal drug metabolising enzymes and P-glycoprotein is far from elucidated. Further insight into the function of these systems may lead to optimisation of drug therapy.
Andersen
V C
VC
Klinisk farmakologisk enhed, Amtssygehuset i Gentofte.
Sonne
J
J
D000818:Animals; D001682:Biological Availability; D003524:Cyclosporins / Q000378:metabolism / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004077:Digoxin / Q000378:metabolism / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D018757:GABA Modulators / Q000378:metabolism / Q000493:pharmacokinetics; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007410:Intestinal Diseases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008874:Midazolam / Q000378:metabolism / Q000493:pharmacokinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D003524:Cyclosporins; D004791:Enzyme Inhibitors; D018757:GABA Modulators; D006023:Glycoproteins; D004364:Pharmaceutical Preparations; D004077:Digoxin; D003577:Cytochrome P-450 Enzyme System; D008874:Midazolam
Tyndtarmens laegemiddelomsaetning--betydning for biotilgaengelighed.