title: In vitro-in situ permeability and dissolution of fexofenadine with kinetic modeling in the presence of sodium dodecyl sulfate.
abstract: The purpose of this study was to estimate passive permeability and efflux transport parameters of fexofenadine (FEX) from in vitro cell culture and in situ rat experiments and determine the dissolution profile of FEX in the absence and presence of sodium dodecyl sulfate (SDS). The dissolution rate of FEX was investigated at different pH values and in the presence of SDS. The permeability of FEX was determined in situ in small intestine of Wistar rats and in vitro in Caco-2 cell monolayer. Permeability of FEX was determined at different donor concentrations, and the effect of SDS at two concentration levels (10 and 50 μM) on FEX permeability was evaluated. The transepithelial electrical resistance values of the in vitro technique were measured to assess monolayer integrity before and after the permeability studies. The FEX permeability parameters in the absence and presence of SDS were estimated using Phoenix WinNonlin software program and compared with other laboratory results for both in vitro and in situ studies. The results showed that FEX has a low permeability in the paracellular permeability as well a potential inhibition of secretion mediated by P-glycoprotein (P(gp)), and its permeability increased with presence of SDS. The dissolution of FEX was pH-dependent and significantly enhanced, especially in the presence of 50 mg SDS.
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Ege University, Izmir, Turkey. Evren.gundogdu@ege.edu.tr
authors.forename: Evren
authors.initials: E
authors.lastname: Gundogdu
authors.forename: V
authors.initials: V
authors.lastname: Mangas-Sanjuan
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonzalez-Alvarez
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
authors.forename: Ercument
authors.initials: E
authors.lastname: Karasulu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D039563:Histamine H1 Antagonists, Non-Sedating / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D039563:Histamine H1 Antagonists, Non-Sedating; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D016593:Terfenadine; C093230:fexofenadine