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Cough Update: Antitussive effect of dextromethorphan in association with CYP2D6 activity

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eMediNexus    05 February 2021

The aim of the study is to test the hypothesis that inhibition of cytochrome P450 2D6 (CYP2D6) by quinidine increases the antitussive effect of dextromethorphan in an induced cough model.

22 healthy extensive metaboliser phenotypes for CYP2D6 were extensively studied according to a randomised, double-blind, cross-over design after administration of: (1) Placebo antitussive headed at 1 hour by placebo inhibitor; (2) 30 mg oral dextromethorphan led at 1 hour by placebo inhibitor (dextromethorphan 30); (3) 60 mg oral dextromethorphan led at 1 hour by placebo inhibitor (dextromethorphan 60); (4) 30 mg oral dextromethorphan headed at 1 hour by 50 mg oral quinidine sulphate (quinidine dextromethorphan 30). Cough frequency which was followed by inhalation of 10% citric acid was measured at baseline and at intervals up to 12 hours.

The results of the study showed inhibition of CYP2D6 by quinidine that caused a significant increase in the mean ratio of dextromethorphan to dextrorphan (DEX: DOR) plasma AUC (96) (0.04 vs 1.81, P<0.001). The mean decrements in cough frequency below baseline over 12 hours were: 8% (11), 17% (14.5), 25% (16.2) and 25% (16.9) for placebo, dextromethorphan 30, dextromethorphan 60 and quinidine dextromethorphan 30 treatments, respectively. Significant differences in antitussive effect were identified for the contrasts between dextromethorphan 60/placebo (P<0.001; 95% CI of difference +80, +327) and quinidine dextromethorphan 30/placebo (P<0.001).

The study concluded that a significant antitussive effect was revealed after 60 mg dextromethorphan and 30 mg dextromethorphan headed by 50 mg quinidine that was used in an induced cough model. It is possible only to indicate a dose effect (30 vs 60 mg) in the antitussive activity of dextromethorphan and improvement of this effect by CYP2D6 inhibition.

Source: Abdul Manap R, Wright CE, Gregory A, et al. The antitussive effect of dextromethorphan in relation to CYP2D6 activity. Br J Clin Pharmacol. 1999 Sep; 48(3):382-7.

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