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Using salt counterions to modify β2-agonist behaviour in vivo

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Using salt counterions to modify β2-agonist behaviour in vivo. / Patel, Aateka; Rudman, Sandra Dhian; Brown, Marc; Hider, Robert Charles; Jones, Stuart Allen; Page, Clive Peter.

In: Molecular Pharmaceutics, Vol. 13, No. 10, 03.10.2016, p. 3439-3448.

Research output: Contribution to journalArticlepeer-review

Harvard

Patel, A, Rudman, SD, Brown, M, Hider, RC, Jones, SA & Page, CP 2016, 'Using salt counterions to modify β2-agonist behaviour in vivo', Molecular Pharmaceutics, vol. 13, no. 10, pp. 3439-3448. https://doi.org/10.1021/acs.molpharmaceut.6b00448

APA

Patel, A., Rudman, S. D., Brown, M., Hider, R. C., Jones, S. A., & Page, C. P. (2016). Using salt counterions to modify β2-agonist behaviour in vivo. Molecular Pharmaceutics, 13(10), 3439-3448. https://doi.org/10.1021/acs.molpharmaceut.6b00448

Vancouver

Author

Patel, Aateka ; Rudman, Sandra Dhian ; Brown, Marc ; Hider, Robert Charles ; Jones, Stuart Allen ; Page, Clive Peter. / Using salt counterions to modify β2-agonist behaviour in vivo. In: Molecular Pharmaceutics. 2016 ; Vol. 13, No. 10. pp. 3439-3448.

Bibtex

@article{a04d94f75bfb48c3ba6796174154c622,
title = "Using salt counterions to modify β2-agonist behaviour in vivo",
abstract = "There 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{\textquoteright}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{\textquoteright}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.",
keywords = "salbutamol, ion-pair, airways, counterion, pharmaceutical salt, 1H2NA",
author = "Aateka Patel and Rudman, {Sandra Dhian} and Marc Brown and Hider, {Robert Charles} and Jones, {Stuart Allen} and Page, {Clive Peter}",
note = "This 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. {\textcopyright} 2016 American Chemical Society.",
year = "2016",
month = oct,
day = "3",
doi = "10.1021/acs.molpharmaceut.6b00448",
language = "English",
volume = "13",
pages = "3439--3448",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Using salt counterions to modify β2-agonist behaviour in vivo

AU - Patel, Aateka

AU - Rudman, Sandra Dhian

AU - Brown, Marc

AU - Hider, Robert Charles

AU - Jones, Stuart Allen

AU - Page, Clive Peter

N1 - This 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.

PY - 2016/10/3

Y1 - 2016/10/3

N2 - There 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.

AB - There 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.

KW - salbutamol

KW - ion-pair

KW - airways

KW - counterion

KW - pharmaceutical salt

KW - 1H2NA

U2 - 10.1021/acs.molpharmaceut.6b00448

DO - 10.1021/acs.molpharmaceut.6b00448

M3 - Article

C2 - 27568865

VL - 13

SP - 3439

EP - 3448

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 10

ER -