Impact of methadone on prolonged QTc time in Methadone Maintenance Treatment (MMT) patients after conversion from chiral (R,S)-methadone to (R)-methadone)

In studies by Anchersen et al. 2009 a subpopulation of MMT patients with prolonged QT-time on ECG has been detected. It has been reported that R-methadone has less effect on QT-time than R,S-methadone. Aim: To investigate serum levels of methadone and QT-time before and three hours after daily R,S-methadone dose in patients at methadone steady state concentrations and with QT-time > 450 ms at inclusion. The patients will then switch to R-methadone (half-dose of R,S-methadone) and at developed concentration of steady state we will again measure methadone serum concentration and QT at Cmin and Cmax of methadone. If R-methadone has less effect on QT-time in these patients they will be offered R-methadone treatment instead of R,S-methadone. The pharmacogenetics regarding metabolizing enzymes (CYP3A4/5, CYP2D6, CYP2B6 and to a lesser degree CYP1A2) in the liver of importance for methadone metabolism will also be investigated in this study.

Collaborators: Mimi Stokke Opdal, MD, PhD; Senior Consultant/Associate prof II; Oslo University Hospital, Dept of Pharmacology