Methadone pharmacology and QTc-time in methadone maintenance treatment patients with end stage kidney failure

Oslo University Hospital is the largest centre for treatment of methadone maintenance treatment (MMT) patients in Norway. This project is performed in collaboration with clinicians at our hospital. In Norway such patients are treated with rather high dose of methadone, around 100 mg daily. Methadone is an opioid that primarily is removed by renal excretion. Some MMT patients develop kidney failure and need treatment with haemodialysis. Methadone treatment has also been associated with increased QT-time giving rise to fatal arrhythmias. Aim: To investigate methadone pharmacokinetics during four hours haemodilaysis in MMT patients with end-stage renal failure, particularly if methadone was removed in haemodialysis or in urine. We investigated possible effects on QT-time by recording ECG every 30 min during haemodialysis. In addition we perform certain clinical tests to assess opioid withdrawal, side effects and clinical impairment along with routine biochemistry tests including pharmacogenetics. Part one of the study was published July 2015 in Clinical Therapeutics. Part two of the study manuscript is under preparation.

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

Publications:

Effects of Hemodialysis on Methadone Pharmacokinetics and QTc.
Opdal MS, Arnesen M, Müller LD, Hullstein I, Sayed K, Brørs O, Kringen M, Sagedal S, Gjesdal K, Krajci P.Clin Ther. 2015 Jul 1;37(7):1594-9. doi: 10.1016/j.clinthera.2015.04.009. Epub 2015 May 8.