title: Transepithelial transport of ambroxol hydrochloride across human intestinal Caco-2 cell monolayers.
abstract: This study aimed i) to characterize the transepithelial transport of the mucolytic agent ambroxol hydrochloride across the intestinal barrier, ii) to classify the ambroxol according to Biopharmaceutics Classification System (BCS) and iii) to predict ambroxol absorption in humans. Transport of ambroxol (100, 300 and 1000 micromol/l) was studied in a human colon carcinoma cell line Caco-2 in apical to basolateral and basolateral to apical direction, under iso-pH 7.4 and pH-gradient (6 vs. 7.4) conditions. The relative contribution of the paracellular route was estimated using Ca2+-free transport medium. Ambroxol samples from receiver compartments were analysed by HPLC with UV detection (242 nm). Results showed that ambroxol transport is linear with time, pH-dependent and direction-independent, displays non-saturable (first-order) kinetics. Thus, the transport seems to be transcellular mediated by passive diffusion. Estimated high solubility and high permeability (P(app) = 45 x 10(-6) cm/s) of ambroxol rank it among well absorbed compounds and class I of BCS. It can be expected that the oral dose fraction of ambroxol absorbed in human intestine is high.
authors.affiliation: Institute of Experimental Biopharmaceutics, Joint Research Centre of the Academy of Sciences of the Czech Republic and PRO.MED.CS Praha a.s., Heyrovského 1207, 500 03 Hradec Králové, Czech Republic. stetinova@uebf.cas.cz
authors.forename: Vera
authors.initials: V
authors.lastname: Stetinová
authors.forename: Libuse
authors.initials: L
authors.lastname: Smetanová
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kholová
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Svoboda
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kvetina
mesh_terms: D000042:Absorption; D000551:Ambroxol / Q000008:administration & dosage / Q000145:classification / Q000493:pharmacokinetics*; D002118:Calcium / Q000172:deficiency; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003110:Colonic Neoplasms / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism*; D005100:Expectorants / Q000008:administration & dosage / Q000145:classification / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D016014:Linear Models; D008954:Models, Biological; D010539:Permeability; D012995:Solubility; D014466:Ultraviolet Rays
chemical_list: D005100:Expectorants; D000551:Ambroxol; D002118:Calcium