title: In-vitro transfer of nitazoxanide across the intestinal epithelial barrier.
abstract: Nitazoxanide is a thiazolide compound that exhibits antimicrobial properties against helminths, protozoa, anaerobic bacteria and also Helicobacter pylori. The mucosal diffusion of this new drug has not been studied. The aim of this study was to examine the transport of radiolabelled nitazoxanide across the epithelial barrier according to the mode (mucosal or serosal) of drug administration. HT29-19A intestinal epithelial cells, grown as monolayers on microporous filters, were used as an epithelial model. In a short-term (100 min) transport study, the apical to basal and the basal to apical transport of nitazoxanide across the monolayers was studied in an Ussing chamber. In a long-term (24 h) study, the transport of the drug and its intracellular accumulation were studied in filter-grown epithelial monolayers kept in culture plates. In the short-term transport study, both the apical and basal fluxes achieved a steady state after 70 min and there was no significant difference between the apical to basal (3991+/-1001 ng h(-1) cm(-2)) and the basal to apical (4246+/-856 ng h(-1) cm(-2)) nitazoxanide fluxes. In the long-term transport study, after apical or basal drug application, a gradual increase in the drug concentration in the opposite compartment was noted, which reached similar values for apical and basal fluxes (2497+/-125 and 2309+/-81 ng mL(-1), respectively) after 24 h. Moreover, a rapid, although transitory, intracellular accumulation of nitazoxanide was observed at 10 min after apical (299+/-25 ng/10(6) cells) and basal (124+/-10 ng/10(6) cells) drug application, but decreased thereafter. There is an important transepithelial transport of nitazoxanide across the digestive epithelial monolayer with a rapid intracellular accumulation of the drug. No difference between the apical to basal and basal to apical fluxes of the drug was observed, suggesting that both topical and systemic modes of action of this antibiotic are successful.
authors.affiliation: INSERM EMI-0212, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris, France. matsiak@necker.fr
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Francis
authors.initials: F
authors.lastname: Mégraud
authors.forename: Martine
authors.initials: M
authors.lastname: Heyman
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002460:Cell Line; D003106:Colon / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004594:Electrophysiology; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D009574:Nitro Compounds; D013844:Thiazoles / Q000493:pharmacokinetics*; D019108:Tight Junctions / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D009574:Nitro Compounds; D013844:Thiazoles; C041747:nitazoxanide