title: Caco-2 cells, biopharmaceutics classification system (BCS) and biowaiver.
abstract: Almost all orally administered drugs are absorbed across the intestinal mucosa. The Caco-2 monolayers are used as an in vitro model to predict drug absorption in humans and to explore mechanism of drug absorption. The Caco-2 cells are derived from a human colon adenocarcinoma and spontaneously differentiate to form confluent monolayer of polarized cells structurally and functionally resembling the small intestinal epithelium. For studying drug permeability, Caco-2 cells are seeded onto the Transwell inserts with semipermeable membrane and grown to late confluence (21 days). After determination of cell viability, the integrity of monolayer is checked by phenol red permeability and by 14C-mannitol permeability. The transport from apical to basolateral (AP-BL) and basolateral to apical (BL-AP) is studied by adding the diluted drug on the apical or basolateral side and withdrawing the samples from the opposite compartment, respectively, for HPLC analysis or liquid scintillation spectrometry. Ca2+ -free transport medium is used to determine paracellular component of the drug transport. On the basis of permeability and solubility, drugs can be categorized into four classes of Biopharmaceutics Classification System (BCS). For certain drugs, the BCS-based biowaiver approach can be used which enables to reduce in vivo bioequivalence studies.
authors.affiliation: Institute of Experimental Biopharmaceutics, Joint Research Centre of PRO.MED.CS Praha. smetanova@uebf.cas.cz
authors.forename: Libuse
authors.initials: L
authors.lastname: Smetanová
authors.forename: Vĕra
authors.initials: V
authors.lastname: Stĕtinová
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Svoboda
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kvetina
mesh_terms: D000284:Administration, Oral; D001692:Biological Transport; D001702:Biopharmaceutics; D018938:Caco-2 Cells; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000145:classification*; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations