Abstract
Preclinical data have shown that high concentrations of the antitussive POV can affect hERG channels in vitro, but do not alter the QT interval even at very high doses/plasma levels in dogs in vivo.
This randomised, placebo-controlled, single-blind, 2-way crossover clinical trial in 18 (9 female and 9 male) healthy volunteers investigated effects of POV on the ECG including the QTc interval following the administration of a supratherapeutic single oral dose of 121.5mg POV (192mg POV citrate in 90ml syrup). This single dose corresponds to the maximum total daily dose recommended for the treatment of dry cough (20mg to 30mg POV up to 4 times daily).
ECGs were continuously recorded over 24h, and triplicate 12-lead ECGs of 10s duration each were extracted. PR, QRS, QT, QTcN, QTcF, and RR intervals as well as heart rate were determined (QTc: QT interval corrected for influences of HR (QTcF=Fridericia formula, QTcN=population method)).
Neither QTcN nor QTcF showed notable findings (new onset of QTc intervals>450ms, changes from baseline in QTc > 30ms) regarding absolute or relative prolongations of the QTc. QTcN and QTcF changes to baseline remained below 2.3 ms throughout the observation period. The highest upper limit of the Confidence Interval of the difference to placebo was 8.5 ms. Also QT, HR, PQ, and QRS did not reveal any relevant findings. No clinically relevant abnormal morphological ECG findings were documented for POV.
POV given as a supratherapeutic single dose (121.5mg, corresponding to 192 mg POV citrate) did not affect the ECG (in particular not the QTc-interval) in healthy subjects.
- © 2014 ERS