Human oral drugs absorption is correlated to their in vitro uptake by brush border membrane vesicles.
Brush border membrane vesicles (BBMV) were prepared from the rabbit small intestine for testing drug absorption potency through the enterocyte's apical membrane, which is an important compartment for drug oral absorption. Some modifications have been made to the traditional vesicle assay for adapting it to the 96-well plate format. The accumulation of 23 reference drugs was measured, and the data showed a good correlation with human oral absorption with a correlation coefficient R=0.853 (P<0.001), with the exception of a few false positive results. As the measured drug absorption may contain a membrane/protein binding component as well as drug uptake into vesicles, these two fractions can be discriminated by changing extravesicular osmolarity using different mannitol concentrations. This model can be applied for evaluating drug absorption rate/mechanisms, and helping drug selection in early drug research and development.
Oulianova
Nathalie
N
Biotechnology Research Institute, National Council of Canada, 6100 Royalmount, Montreal, Quebec H4P 2R2, Canada.
Cheng
Deping
D
Huebert
Norman
N
Chen
Yanmin
Y
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001390:Azlocillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D002434:Cefadroxil / Q000008:administration & dosage / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D019259:Lamivudine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008353:Mannitol / Q000737:chemistry; D009994:Osmolar Concentration; D010042:Ouabain / Q000008:administration & dosage / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D010637:Phenolsulfonphthalein / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics
D004364:Pharmaceutical Preparations; D002434:Cefadroxil; D019259:Lamivudine; D000082:Acetaminophen; D008353:Mannitol; D015215:Zidovudine; D010042:Ouabain; D004317:Doxorubicin; D001390:Azlocillin; D010637:Phenolsulfonphthalein