Duration of Action of Dextromethorphan
Dextromethorphan has a duration of action of 4-6 hours for standard immediate-release formulations, while extended-release polistirex formulations provide approximately 12 hours of cough suppression. 1, 2
Standard Immediate-Release Formulations
The immediate-release formulations of dextromethorphan demonstrate the following pharmacodynamic profile:
- Duration of effect: 4-6 hours after oral administration 1
- Onset of action occurs within 15-30 minutes of dosing 1
- Peak plasma concentrations are reached within 1-3 hours 1
- The therapeutic plasma concentration range is 10-40 ng/mL 3
This relatively short duration necessitates multiple daily dosing (typically every 4-6 hours) to maintain consistent cough suppression throughout the day. 1
Extended-Release Polistirex Formulation
The polistirex formulation (marketed as Delsym®) provides significantly prolonged action:
- Duration of action: approximately 12 hours (labeled as "12 Hour Cough Relief") 2
- The polistirex binder slows the release of active dextromethorphan by 2-3 times compared to standard formulations 3
- Once liberated from the binder, the dextromethorphan itself has unchanged pharmacokinetics and clinical effects 3
- This extended duration allows for twice-daily dosing rather than every 4-6 hours 2
Clinical Evidence from Controlled Trials
Multiple controlled studies have evaluated dextromethorphan's duration in various patient populations:
- In patients with chronic bronchitis, a single 60 mg dose reduced cough counts by 50% for the duration of the study period 1
- In patients with upper respiratory infections, 30 mg doses showed significant cough frequency reduction at 1 hour post-dose 1
- The antitussive effect was maintained throughout the 4-6 hour observation period in most studies 1
Important Clinical Considerations
The duration of action can be significantly prolonged when dextromethorphan is combined with CYP2D6 inhibitors like quinidine, which suppress the O-demethylation of dextromethorphan and increase plasma concentrations. 4 This combination can extend the duration of effect but is used for different therapeutic indications (pseudobulbar affect, depression) rather than cough suppression. 5, 4
In overdose situations, particularly with the polistirex formulation, the duration of toxic effects can extend well beyond 12 hours due to continued drug release from the binder, requiring prolonged monitoring and supportive care. 3