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Methadone, which can be associated with QTc prolongation, torsades, and sudden death, commonly is prescribed as a mixture of (S)-methadone and (R)-methadone. The (R) isomer has substantially stronger activity on the µ-opioid receptor and has much greater analgesic potency; the (S) form interacts with channels responsible for QTc prolongation. In this prospective study, 39 opioid-dependent patients in Germany and Switzerland were treated sequentially with (R,S)-methadone and (R)-methadone; each treatment lasted 14 days. Because (R)-methadone has greater potency, it was administered at half-dose.
When (R,S)-methadone was replaced by (R)-methadone, QTc intervals decreased by a mean of –3.9 milliseconds weekly. When (R)-methadone was replaced by…