title: Transintestinal secretion of ciprofloxacin, grepafloxacin and sparfloxacin: in vitro and in situ inhibition studies.
abstract: The influence of the secretion process on the absorption of ciprofloxacin, grepafloxacin and sparfloxacin has been evaluated by means of inhibition studies. Two well known P-glycoprotein inhibitors (cyclosporine, verapamil), a mixed inhibitor of P-glycoprotein and the organic cation transporter OCT1 (quinidine) and a well established MRP substrate (p-aminohipuric acid) have been selected in order to distinguish the possible carriers implicated. An in situ rat gut perfusion model and CACO-2 permeability studies are used. Both methods suggest the involvement of several types of efflux transporters for every fluoroquinolone. The relevance of the secretory pathway depends on the intrinsic permeability of the quinolone. The in vitro model seems to be more suitable for discriminating mechanisms underlying the absorption process, while in situ studies are less sensitive to inhibition studies.
authors.affiliation: Department of Pharmacy and Pharmaceutics, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Ibáñez
authors.forename: R
authors.initials: R
authors.lastname: Nalda-Molina
authors.forename: M
authors.initials: M
authors.lastname: Montalar-Montero
authors.forename: M V
authors.initials: MV
authors.lastname: Bermejo
authors.forename: V
authors.initials: V
authors.lastname: Merino
authors.forename: T M
authors.initials: TM
authors.lastname: Garrigues
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D004337:Drug Carriers; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D010879:Piperazines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers; D024841:Fluoroquinolones; D010879:Piperazines; D002939:Ciprofloxacin; C075375:grepafloxacin; C061363:sparfloxacin