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Effects of switching from racemic methadone to R-methadone on serum methadone concentrations and QTc intervals
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cross over study before and after drug switch | Other | Stabilized on racemic methadone dose, switched to R-methadone of half racemic methadone dose. Cross over study, own control |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Same individuals treated with racemic methadone and switched to levomethadone (R-methadone) | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effects of switching from racemic methadone to R-methadone on serum methadone concentrations. | 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). | Time frame of each patient form inclusion to end study was 35-40 days. |
| Effects of switching from racemic methadone to R-methadone on QTc interval | 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. | Time frame of each patient form inclusion to end study was 35-40 days. |
| Effects of switching from racemic methadone to R-methadone on opioid withdrawal symptoms (OWS) | Ten patients: each patients had OWS recorded on racemic and R-methadone treatment using OWS. | Time frame of each patient form inclusion to end study was 35-40 days. |
| Effects of switching from racemic methadone to R-methadone, stability of serum electrolytes (Ca, Mg, K) in patients | 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) | Time frame of each patient form inclusion to end study was 35-40 days. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mimi Stokke S Opdal, MD, PhD | Oslo University Hospital and University of Oslo | Study Director |
| Peter Krajci, MD, PhD | Oslo University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Pharmacology , Oslo University Hospital | Oslo | 0424 | Norway | |||
| Department of Pharmacology and Department of Substance Use Disorder, Oslo University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38308508 | Background | Havig SM, Berg-Pedersen RM, Krabseth HM, Muller LD, Haugaa K, Zare HK, Gjesdal K, Krajci P, Opdal MS. Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients. Basic Clin Pharmacol Toxicol. 2024 Apr;134(4):519-530. doi: 10.1111/bcpt.13982. Epub 2024 Feb 3. |
| Label | URL |
|---|---|
| abstract from EACPT 2019, see abstract 1168 | View source |
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IPD can be shared when the manuscript has been accepted for publication.
Protocol in Norwegian attached
IPD proving the results of the different outcome measures will be shared, see above
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 23, 2012 | Jan 29, 2020 | Prot_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 7, 2015 | Jan 29, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D001145 | Arrhythmias, Cardiac |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
| D013678 | Technology, Pharmaceutical |
| D008919 | Investigative Techniques |
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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.
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| Oslo |
| 0424 |
| Norway |
| Department of Substance Use Disorder, Oslo University Hospital | Oslo | 0424 | Norway |
| D013568 | Pathological Conditions, Signs and Symptoms |