Methadone-maintained volunteers experienced moderately severe opiate withdrawal symptoms within 3 or 4 days of beginning phenytoin in therapeutic doses. The area under the methadone plasma concentration-time curve decreased while the ratio of the pyrrolidine-to-metabolite excretion in urine to this area increased significantly. This suggests that phenytoin accelerates methadone metabolism. Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients.

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