Characterisation of cough evoked by inhaled treprostinil and treprostinil palmitil.
Autor: | Chapman RW; Insmed Incorporated, Bridgewater, NJ, USA., Corboz MR; Insmed Incorporated, Bridgewater, NJ, USA., Fernandez C; Insmed Incorporated, Bridgewater, NJ, USA., Sullivan E; Insmed Incorporated, Bridgewater, NJ, USA., Stautberg A; Insmed Incorporated, Bridgewater, NJ, USA., Plaunt AJ; Insmed Incorporated, Bridgewater, NJ, USA., Konicek DM; Insmed Incorporated, Bridgewater, NJ, USA., Malinin V; Insmed Incorporated, Bridgewater, NJ, USA., Li Z; Insmed Incorporated, Bridgewater, NJ, USA., Cipolla D; Insmed Incorporated, Bridgewater, NJ, USA., Perkins W; Insmed Incorporated, Bridgewater, NJ, USA. |
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Jazyk: | angličtina |
Zdroj: | ERJ open research [ERJ Open Res] 2021 Feb 15; Vol. 7 (1). Date of Electronic Publication: 2021 Feb 15 (Print Publication: 2021). |
DOI: | 10.1183/23120541.00592-2020 |
Abstrakt: | Cough is induced by inhaled prostacyclin analogues including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved in TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS). Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously. In guinea pigs, cough with inhaled TRE (1.23 µg·kg -1 ) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg -1 ) to induce cough. TRE cough was blocked with IP and tachykinin NK Competing Interests: Conflict of interest: R.W. Chapman is an employee of Insmed Incorporated. Conflict of interest: M.R. Corboz is an employee of Insmed Incorporated. Conflict of interest: C. Fernandez is an employee of Insmed Incorporated. Conflict of interest: E. Sullivan is an employee of Insmed Inc. Conflict of interest: A. Stautberg is an employee of Insmed Incorporated. Conflict of interest: A.J. Plaunt is an employee of Insmed Incorporated. In addition, he has patents pending or issued (patent numbers US 10,010,518, US 10,526,274, US 9,255,064 and US 9,469,600) related to treprostinil palmitil and methods of treatment via administration of treprostinil palmitil. Conflict of interest: D.M. Konicek is an employee of Insmed Incorporated. In addition, she has patents pending or issued (patent numbers US 10,010,518, US 10,526,274, US 9,255,064 and US 9,469,600) related to treprostinil palmitil and methods of treatment via administration of treprostinil palmitil. Conflict of interest: V. Malinin is an employee of Insmed Incorporated. In addition, he has patents pending or issued(patent numbers US 10,010,518, US 10,526,274, US 9,255,064 and US 9,469,600) related to treprostinil palmitil and methods of treatment via administration of treprostinil palmitil. Conflict of interest: Z. Li is an employee of Insmed Incorporated. In addition, he has patents pending or issued(patent numbers US 10,010,518, US 10,526,274, US 9,255,064 and US 9,469,600) related to treprostinil palmitil and methods of treatment via administration of treprostinil palmitil. Conflict of interest: D. Cipolla is an employee of Insmed Incorporated. Conflict of interest: W. Perkins is an employee of Insmed Incorporated. In addition, he has patents pending or issued(patent numbers US 10,010,518, US 10,526,274, US 9,255,064 and US 9,469,600) related to treprostinil palmitil and methods of treatment via administration of treprostinil palmitil. (Copyright ©ERS 2021.) |
Databáze: | MEDLINE |
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