Antitussive Effect of Dextromethorphan and Dextromethorphan-Salbutamol Combination in Healthy Volunteers with Artificially Induced Cough

Karttunen, P; Tukiainen, H; Silvasti, M; Kolonen, Sakari

doi:10.1159/000195303

Cited by 17 publications

(10 citation statements)

References 7 publications

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“…In this study the assessment of the cough reflex with citric acid demonstrated a statistically significant and consistent decrease in sensitivity associated with dextromethorphan administration when compared with placebo. This robust drug effect is consistent with several other studies performed using citric acid cough challenge methodology in normal subjects [1–3, 7, 16, 17]. There can be little doubt that dextromethorphan in the preparation used alters the cough reflex sensitivity and this study shows that such a change in cough reflex and sensitivity can be demonstrated in a population with chronic cough.…”

Section: Discussionsupporting

confidence: 91%

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

Ramsay

Wright

Thompson

et al. 2008

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Dextromethorphan is widely used as a cough suppressant in over the counter medications.• Its efficacy in altering cough reflex sensitivity has been shown in healthy volunteers. In contrast evidence for an effect on clinically important cough is poor. WHAT THIS STUDY ADDS• A significant decrease in evoked cough was seen with dextromethorphan compared with placebo. However, both placebo and active treatment improved subjective data to a similar degree.• We doubt the validity of currently used objective tests in the investigation of antitussives. AIMSUsing an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo. METHODSThe study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml -1 dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose-response cough challenge. RESULTSDextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked 'placebo' effect. CONCLUSIONSThe objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences.

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Section: Discussionsupporting

confidence: 91%

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

Ramsay

Wright

Thompson

et al. 2008

Brit J Clinical Pharma

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“…Both treatments were significantly superior to placebo in reduction of overall cough frequency (P , 0.0001) for up to 8 hours posttreatment. Similarly, Karttunen et al (1987) reported the antitussive effects of dextromethorphan (30 mg) plus salbutamol (2 mg), dextromethorphan (30 mg) alone, or placebo. Significant increases in cough threshold were shown after dextromethorphan and the dextromethorphan-salbutamol combination.…”

Section: B Dextromethorphanmentioning

confidence: 99%

Antitussive Drugs—Past, Present, and Future

et al. 2014

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“…DEX, a codeine analogue devoid of opiate side‐effects, is widely available over the counter as a cough suppressant. Its effectiveness has been confirmed in both clinical [3, 9–13] and experimental cough challenge studies [14, 15]. The metabolism of DEX is largely by CYP2D6‐mediated O‐demethylation to DOR.…”

Section: Introductionmentioning

confidence: 97%

Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: dextromethorphan vs. dextrorphan using quinidine inhibition

Moghadamnia

Rostami‐Hodjegan

Abdul-Manap

et al. 2003

Brit J Clinical Pharma

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Aims To define the relative antitussive effect of dextromethorphan (DEX) and its primary metabolite dextrorphan (DOR) after administration of DEX. Methods Data were analysed from a double-blind, randomized cross-over study in which 22 subjects received the following oral treatments: (i) placebo; (ii) 30 mg DEX hydro-bromide; (iii) 60 mg DEX hydro-bromide; and (iv) 30 mg DEX hydrobromide preceded at 1 h by quinidine HCl (50 mg). Cough was elicited using citric acid challenge. Pharmacokinetic data from all non-placebo arms of the study were fitted simultaneously. The parameters were then used as covariates in a link PK-PD model of cough suppression using data from all treatment arms. Results The best-fit PK model assumed two-and one-compartment PK models for DEX and DOR, respectively, and competitive inhibition of DEX metabolism by quinidine. The intrinsic clearance of DEX estimated from the model ranged from 59 to 1536 l h -1 , which overlapped with that extrapolated from in vitro data (12-261 l h -1 ) and showed similar variation (26-vs. 21-fold, respectively). The inhibitory effect of quinidine ([I]/Ki) was 19 (95% confidence interval of mean: 18-20) with an estimated average Ki of 0.017 m M. Although DEX and DOR were both active, the potency of the antitussive effect of DOR was 38% that of DEX. A sustained antitussive effect was related to slow removal of DEX/DOR from the effect site (k e0 = 0.07 h -1 ). Conclusions Physiologically based PK modelling with perturbation of metabolism using an inhibitor allowed evaluation of the antitussive potency of DOR without the need for separate administration of DOR.

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Antitussive Effect of Dextromethorphan and Dextromethorphan-Salbutamol Combination in Healthy Volunteers with Artificially Induced Cough

Cited by 17 publications

References 7 publications

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

Antitussive Drugs—Past, Present, and Future

Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: dextromethorphan vs. dextrorphan using quinidine inhibition

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