Dextromethorphan is a dextro-isomer of levorphanol, which is a non-narcotic codeine analogue. In humans, orally administered dextromethorphan has shown to have a significant reduction in frequency of cough in patients with chronic pathological cough.

A related efficacy in experimentally induced cough in individuals using a citric acid aerosol was demonstrated. Dextromethorphan demonstrates polymorphic metabolism through the enzyme P4502D6, with 10-20% of the population as slow metabolizers. In a fast metabolizer’s population, dextromethorphan is rapidly O-demethylated by the liver to a projected active metabolite dextrorphan known to also have antitussive activity. A peak plasma level of dextromethorphan happens approximately 2 hours after oral administration and it has a half-life of 2.5-3.9 hours.

Dextromethorphan is broadly used as an antitussive agent having a non-narcotic codeine analogue. An investigation was conducted to assess whether the inhaled administration of dextromethorphan delivers antitussive activity in a cough model induced by citric acid. Twenty normal individuals undertook repeated cough challenge with 5% citric acid. Participants were studied on six different occasions. Study medication containing oral dextromethorphan 30 mg or oral placebo or 1, 3 and 30 mg inhaled dextromethorphan or inhaled matched placebo.

Cough challenge was directed 10 minutes after the study medication and hourly subsequently up to 250 minutes. No significant differences were observed in baseline cough responses. Oral dextromethorphan (i.e. 30 mg) produced a mean percentage decrease in cough of 38% that remained significant at 250 minutes. The antitussive effect of oral dextromethorphan was confirmed with extended inhibition of induced cough. The study concluded that oral dextromethorphan is a potent and long lasting antitussive agent; however the inhaled drug does not produce any significant reduction in the cough reflex.

Source: Grattan TJ, Marshall AE, Higgins KS, Morice AH. The effect of inhaled and oral dextromethorphan on citric acid induced cough in man. Br J Clin Pharmacol. 1995 Mar; 39(3):261-3