Comparing metoclopramide electrotransport kinetics in vitro and in vivo

Article Article scientifique Article Comparing metoclopramide electrotransport kinetics in vitro and in vivo eng 2010 author Cazares Delgadillo Jennyfer 636096 author Benaziza Ines 539976 author Balaguer-Fernández Cristina author Calatayud-Pascual Aracely author Ganem-Rondero Adriana author Quintanar-Guerrero David author Castellano Alicia C López author Merino Virginia author Kalia Yogeshvar 0000-0001-9049-5489 503798 353-359 10.1016/j.ejps.2010.07.006 20633643 0928-0987 The purpose of this work was to investigate the transdermal iontophoretic delivery of metoclopramide and to determine (i) the dependence of electrotransport on current density and drug concentration, (ii) the relative contributions of electromigration and electroosmosis and (iii) the feasibility of administering therapeutic amounts of drug, using a drug-sparing iontophoretic configuration. Iontophoretic delivery of metoclopramide (MCL) across dermatomed porcine ear skin was investigated in vitro as a function of concentration (10, 20, 40, 80 and 100mM) and current density (0.1, 0.2 and 0.3mAcm(-2)) using vertical flow-through diffusion cells. In vivo studies were performed in Wistar rats (40mM MCL, 0.3mAcm(-2), 5h); the anodal and drug formulation compartments were separated by a salt bridge. Cumulative delivery in vitro after 7h of current application (40mM MCL; 0.3mAcm(-2)) in the absence of electrolyte was 624.45+/-99.45microgcm(-2) (flux - 2.55+/-0.35microgcm(-2)min(-1)). There was a linear relationship between flux and both current density and drug concentration. Co-iontophoresis of acetaminophen confirmed that electromigration was the major transport mechanism (accounting for approximately 80% of MCL delivery). Electroosmotic inhibition, albeit modest, was only observed at the highest MCL concentration (100mM). Although the delivery rate observed in vivo in male Wistar rats (1.21+/-0.55microgcm(-2)min(-1)) was lower than that observed in vitro, the results suggest that drug input rates would be sufficient to achieve therapeutic levels in humans using non-invasive transdermal iontophoresis. Animals Antiemetics/pharmacokinetics Male Metoclopramide/pharmacokinetics Rats Rats, Wistar Swine Dewey 615 31 Section des sciences pharmaceutiques 17 false European journal of pharmaceutical sciences 41 2 c8941969-a0fc-4e99-be28-7b863fd3dd0f Article (Accepted version) Restricted 10 Cazares EJPS-2.pdf 385358 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Comparing metoclopramide electrotransport kinetics in vitro and in vivo	European journal of pharmaceutical sciences			2010	607	1

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