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dc.contributor.author
Novak, Analia
dc.contributor.author
Delli Carpini, Griselda
dc.contributor.author
Ruiz, Maria Laura
dc.contributor.author
Luquita, Marcelo Gabriel
dc.contributor.author
Rubio, Modesto Carlos
dc.contributor.author
Mottino, Aldo Domingo
dc.contributor.author
Ghanem, Carolina Inés
dc.date.available
2016-06-09T16:16:16Z
dc.date.issued
2013-10
dc.identifier.citation
Novak, Analia; Delli Carpini, Griselda; Ruiz, Maria Laura; Luquita, Marcelo Gabriel; Rubio, Modesto Carlos; et al.; Acetaminophen Inhibits Intestinal P-Glycoprotein Transport Activity; Wiley; Journal of Pharmaceutical Sciences; 102; 10; 10-2013; 3830-3837
dc.identifier.issn
0022-3549
dc.identifier.uri
http://hdl.handle.net/11336/6126
dc.description.abstract
Repeated acetaminophen (AP) administration modulates intestinal P-glycoprotein (P-gp) expression. Whether AP can modulate P-gp activity in a short-term fashion is unknown. We investigated the acute effect of AP on rat intestinal P-gp activity in vivo and in vitro. In everted intestinal sacs, AP inhibited serosal-mucosal transport of rhodamine 123 (R123), a prototypical P-gp substrate. R123 efflux plotted against R123 concentration adjusted well to a sigmoidal curve. Vmax decreased 50% in the presence of AP, with no modification in EC50, or slope, ruling out the possibility of inhibition to be competitive. Inhibition by AP was absent at 0°C, consistent with interference of the active transport of R123 by AP. Additionally, AP showed no effect on normal localization of P-gp at the apical membrane of the enterocyte and neither affected paracellular permeability. Consistent with absence of a competitive inhibition, two further strategies strongly suggested that AP is not a P-gp substrate. First, serosal-mucosal transport of AP was not affected by the classical P-gp inhibitors verapamil or Psc 833. Second, AP accumulation was not different between P-gp knock-down and wild-type HepG2 cells. In vivo intestinal absorption of digoxin, another substrate of P-gp, was assessed in the presence or absence of AP (100 μM). Portal digoxin concentration was increased by 214%, in average, by AP, as compared with digoxin alone. In conclusion, AP inhibited P-gp activity, increasing intestinal absorption of digoxin, a prototypical substrate. These results suggest that therapeutic efficacy of P-gp substrates can be altered if coadministered with AP.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Acetaminophen
dc.subject
P-Glycoprotein
dc.subject
Interaction
dc.subject.classification
Gastroenterología y Hepatología
dc.subject.classification
Medicina Clínica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Acetaminophen Inhibits Intestinal P-Glycoprotein Transport Activity
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-06-01T13:33:34Z
dc.journal.volume
102
dc.journal.number
10
dc.journal.pagination
3830-3837
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Novak, Analia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
dc.description.fil
Fil: Delli Carpini, Griselda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
dc.description.fil
Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Rubio, Modesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina
dc.description.fil
Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Ghanem, Carolina Inés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina
dc.journal.title
Journal of Pharmaceutical Sciences
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jps.23673/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1002/jps.23673
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/jps.23673


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