CYP2D6 polymorphism and the anti-tussive effect of dextromethorphan in man

C. E. Wright, Roslina Abd. Manap, S. Melor, A. H. Morice

Research output: Contribution to journalArticle

Abstract

Dextromethorphan (DEX) is a potent and widely used anti-tussive agent, which undergoes CYP2D6 dependent metabolism in the liver to dextrophan (Kerry et al ). 1 in 10 of the population is defective in the CYP2D6 enzyme (poor metabolisers). By using quinidine to inhibit CYP2D6 in extensive metabolisers (EM's) we have investigated whether differences in the metabolism of dextromethorphan influence evoked cough. Using a cross-over, double-blind, placebo-controlled design 22 EM's, 12 male, 10 female were studied on four separate occasions (1) after placebo (2) after 30 mg DEX (3) after 50 mg quinidine 1 hour before 30 mg DEX (4) after 60 mg DEX. Cough response over 1 minute following each of 5 citric acid inhalations (10% citric acid delivered as 1 s nebulisation through breath activated dosimeter) was measured predose and 1, 2,3,4,6, 8, 10 and 12 hours after dosing with DEX. The % decrease in cough from baseline for each treatment group was compared using mean area under the curve (AUC). Placebo produced a 9% reduction in cough. DEX (30 mg) produced a significant (p<0.05) 17% reduction compared to placebo. DEX (60 mg ) and 50 mg quinidine plus DEX (30 mg) produced similar significant reductions in cough of 25 (p< 0.01). The median time to peak anti-tussive effect of DEX (60 mg) was t=180 min compared to DEX (30 mg) and quinidine 50mg plus DEX (30 mg ) t= 240 min . In all cases the anti-tussive effect of DEX was still significant at t=720 min. Inhibition of CYP2D6 enhanced dextromethorphan's antitussive effect, indicating that the genetic polymorphism in CYP2D6 may have a clinically important influence on the pharmacological activity of this agent.

Original languageEnglish
JournalThorax
Volume52
Issue numberSUPPL. 6
Publication statusPublished - Dec 1997
Externally publishedYes

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Dextromethorphan
Cytochrome P-450 CYP2D6
Cough
Quinidine
Placebos
Citric Acid
Antitussive Agents
Genetic Polymorphisms

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Wright, C. E., Abd. Manap, R., Melor, S., & Morice, A. H. (1997). CYP2D6 polymorphism and the anti-tussive effect of dextromethorphan in man. Thorax, 52(SUPPL. 6).

CYP2D6 polymorphism and the anti-tussive effect of dextromethorphan in man. / Wright, C. E.; Abd. Manap, Roslina; Melor, S.; Morice, A. H.

In: Thorax, Vol. 52, No. SUPPL. 6, 12.1997.

Research output: Contribution to journalArticle

Wright, CE, Abd. Manap, R, Melor, S & Morice, AH 1997, 'CYP2D6 polymorphism and the anti-tussive effect of dextromethorphan in man', Thorax, vol. 52, no. SUPPL. 6.
Wright, C. E. ; Abd. Manap, Roslina ; Melor, S. ; Morice, A. H. / CYP2D6 polymorphism and the anti-tussive effect of dextromethorphan in man. In: Thorax. 1997 ; Vol. 52, No. SUPPL. 6.
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