Show simple item record

dc.contributor.authorPatel, Aateka
dc.contributor.authorKeir, Sandra D
dc.contributor.authorHider, Robert
dc.contributor.authorJones, Stuart A
dc.contributor.authorPage, Clive P
dc.contributor.authorBrown, Marc
dc.date.accessioned2017-06-27T15:44:09Z
dc.date.available2017-06-27T15:44:09Z
dc.date.issued2016-10-03
dc.identifier.citationPatel , A , Keir , S D , Hider , R , Jones , S A , Page , C P & Brown , M 2016 , ' Using Salt Counterions to Modify β2-Agonist Behavior in Vivo ' , Molecular Pharmaceutics , vol. 13 , no. 10 , pp. 3439-3448 . https://doi.org/10.1021/acs.molpharmaceut.6b00448
dc.identifier.issn1543-8384
dc.identifier.otherPURE: 11125852
dc.identifier.otherPURE UUID: a04d94f7-5bfb-48c3-ba67-96174154c622
dc.identifier.otherPubMed: 27568865
dc.identifier.otherScopus: 84989916605
dc.identifier.urihttp://hdl.handle.net/2299/18584
dc.descriptionThis is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. © 2016 American Chemical Society.
dc.description.abstractThere is a paucity of data describing the impact of salt counterions on the biological performance of inhaled medicines in vivo. The aim of this study was to determine if the coadministration of salt counterions influenced the tissue permeability and airway smooth muscle relaxation potential of salbutamol, formoterol, and salmeterol. The results demonstrated that only salbutamol, when formulated with an excess of the 1-hydroxy-2-naphthoate (1H2NA) counterion, exhibited a superior bronchodilator effect (p < 0.05) compared to salbutamol base. The counterions aspartate, maleate, fumarate, and 1H2NA had no effect on the ability of formoterol or salmeterol to reduce airway resistance in vivo. Studies using guinea pig tracheal sections showed that the salbutamol:1H2NA combination resulted in a significantly faster (p < 0.05) rate of tissue transport compared to salbutamol base. Furthermore, when the relaxant activity of salbutamol was assessed in vitro using electrically stimulated, superfused preparations of guinea pig trachea, the inhibition of contraction by salbutamol in the presence of 1H2NA was greater than with salbutamol base (a total inhibition of 94.13%, p < 0.05). The reason for the modification of salbutamol's behavior upon administration with 1H2NA was assigned to ion-pair formation, which was identified using infrared spectroscopy. Ion-pair formation is known to modify a drug's physicochemical properties, and the data from this study suggested that the choice of counterion in inhaled pharmaceutical salts should be considered carefully as it has the potential to alter drug action in vivo.en
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofMolecular Pharmaceutics
dc.rightsOpen
dc.subjectsalbutamol
dc.subjection-pair
dc.subjectairways
dc.subjectcounterion
dc.subjectpharmaceutical salt
dc.subject1H2NA
dc.titleUsing Salt Counterions to Modify β2-Agonist Behavior in Vivoen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Pharmacy, Pharmacology and Postgraduate Medicine
dc.contributor.institutionCentre for Research into Topical Drug Delivery and Toxicology
dc.contributor.institutionPharmaceutics
dc.contributor.institutionSkin and Nail Group
dc.contributor.institutionAirway Group
dc.contributor.institutionBioadhesive Drug Delivery Group
dc.contributor.institutionNanopharmaceutics
dc.contributor.institutionPharmaceutical Analysis and Product Characterisation
dc.contributor.institutionToxicology
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2016-10-03
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1021/acs.molpharmaceut.6b00448
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record