Adverse Drug Effect, Drug Effect, Heart Arrhythmia
Conditions
Keywords
Racemic methadone, R-methadone, QTc interval, Methadone maintenance treatment patients
Brief summary
Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals
Detailed description
Racemic methadone may prolong the QTc interval, which is associated with fatal arrhythmias. In vitro studies have shown that R-methadone has less inhibitory effect than S-methadone on the voltage-gated potassium channel current, and is thus thought to have less effect on the QTc interval. The investigators hypothesized that switching from racemic to R-methadone would reduce the methadone serum concentration and also its effect on the QTc interval.
Interventions
DRUGSame individuals treated with racemic methadone and switched to levomethadone (R-methadone)
Sponsors
Oslo University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients included were stabilized on per os methadone maintenance treatment and had automatically ECG recorded QTc interval greater or equal to 450 ms. The patients were switched to pure R-methadone per os (half dose of the racemic methadone used). Doses, serum drug concentrations, QTc-time were recorded before and after drug switch. Serum-electrolytes (Mg, K, Ca) and opioid withdrawal symptom scale (OWS) were also measured and scored before and after drug switch.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Stabilized on daily methadone dose * Not using other drugs of abuse * QTc-time recorded automatically, patient inclusion if QTc interval was greater or equal to 450 ms * Older than 18 years * Can sign and understand a written Consent
Exclusion criteria
* Can not cooperate regarding observed daily drug intake * Serious psychiatric disease * Untreated serious somatic disease * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of switching from racemic methadone to R-methadone on serum methadone concentrations. | Time frame of each patient form inclusion to end study was 35-40 days. | Ten patients stabilized on racemic methadone dose were switched to R-methadone and effects on serum methadone concentrations were studied. Methadone concentrations (nmol/L) were measured by validated high pressure liquid chromatography coupled to mass spectrometry detection (LC-MSMS). |
| Effects of switching from racemic methadone to R-methadone on QTc interval | Time frame of each patient form inclusion to end study was 35-40 days. | In ten patients QTc intervals were recorded on racemic methadone treatment at Cmin and Cmax of methadone drug concentrations and likewise after the shift to R-methadone. QT intervals (ms) on ECG were recorded automatically and read manually by experienced cardiologists. |
| Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS) | Time frame of each patient form inclusion to end study was 35-40 days. | Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS. |
| Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients | Time frame of each patient form inclusion to end study was 35-40 days. | Ten patients: samples for serum electrolytes were collected before and after switch to R-methadone. Measured by routine analysis at Cobas 8000 (unit mmol/L) |
Countries
Norway
Outcome results
None listed