title: Permeation of four oral drugs through human intestinal mucosa.
abstract: The pharmaceutical industry is in need of rapid and accurate methods to screen new drug leads for intestinal permeability potential in the early stages of drug discovery. Excised human jejunal mucosa was used to investigate the permeability of the small intestine to four oral drugs, using a flow-through diffusion system. The four drugs were selected as representative model compounds of drug classes 1 and 3 according to the biopharmaceutics classification system (BCS). The drugs selected were zidovudine, propranolol HCl, didanosine, and enalapril maleate. Permeability values from our in vitro diffusion model were compared with the BCS permeability classification and in vivo and in vitro gastrointestinal drug permeability. The flux rates of the four drugs were influenced by the length of the experiment. Both class 1 drugs showed a significantly higher mean flux rate between 2 and 6 h across the jejunal mucosa compared to the class 3 drugs. The results are therefore in line with the drugs' BCS classification. The results of this study show that the permeability values of jejunal mucosa obtained with the flow-through diffusion system are good predictors of the selected BCS class 1 and 3 drugs' permeation, and it concurred with other in vitro and in vivo studies.
authors.affiliation: Medical Microbiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa. ebasson@sun.ac.za
authors.forename: Erina
authors.initials: E
authors.lastname: Pretorius
authors.forename: Patrick J D
authors.initials: PJ
authors.lastname: Bouic
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016049:Didanosine / Q000008:administration & dosage / Q000378:metabolism*; D004058:Diffusion; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004656:Enalapril / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011433:Propranolol / Q000008:administration & dosage / Q000378:metabolism*; D015203:Reproducibility of Results; D012995:Solubility; D015215:Zidovudine / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D015215:Zidovudine; D004656:Enalapril; D011433:Propranolol; D016049:Didanosine