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This entry refers to the therapeutic switch from racemic methadone to levomethadone (the R-enantiomer of methadone) investigated by Oslo University Hospital in the MePhaCard clinical trial. Racemic methadone is a 50:50 mixture of R- and S-enantiomers used for methadone maintenance treatment (MMT) in patients with opioid dependence. While both enantiomers contribute to mu-opioid receptor agonism, the S-enantiomer is primarily responsible for the inhibition of the hERG potassium channel, which can lead to significant QTc interval prolongation and increased cardiac risk. Levomethadone (R-methadone) retains the therapeutic efficacy for opioid use disorder but has a significantly lower inhibitory effect on the hERG channel. The Oslo University Hospital study evaluates whether switching patients with prolonged QTc intervals from racemic methadone to equipotent doses of levomethadone can normalize cardiac rhythm while maintaining stabilization of opioid dependence.
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