Shoaib Faruqi
A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers
Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H.
Authors
Caroline Wright
Rachel Thompson
Professor Alyn Morice A.H.Morice@hull.ac.uk
Foundation Chair and Professor of Respiratory Medicine
Abstract
AIMS The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers.METHODS In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships.RESULTS Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate.CONCLUSIONS We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses.
Citation
Faruqi, S., Wright, C., Thompson, R., & Morice, A. H. (2014). A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers. British Journal of Clinical Pharmacology, 78(6), 1272-1280. https://doi.org/10.1111/bcp.12458
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 27, 2014 |
Online Publication Date | Jul 4, 2014 |
Publication Date | 2014-12 |
Deposit Date | May 26, 2022 |
Journal | British Journal of Clinical Pharmacology |
Print ISSN | 0306-5251 |
Electronic ISSN | 1365-2125 |
Publisher | British Pharmacological Society |
Peer Reviewed | Peer Reviewed |
Volume | 78 |
Issue | 6 |
Pages | 1272-1280 |
DOI | https://doi.org/10.1111/bcp.12458 |
Keywords | Butamirate; Capsaicin; Cough sensitivity; Dextromethorphan |
Public URL | https://hull-repository.worktribe.com/output/3610088 |
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