THE EFFECT OF THE LIVER ON THE METABOLISM OF d,l-METHADONE IN VITRO AND IN VIVO

1. Liver was found to be the chief organ for metabolizing d,l-methadone in rats by incubation studies with tissue slices. 2. The optimum pH was found to be between 7.5 and 8.5. Oxygen was found to be essential. Hydroxylamine, azide, cysteine, glutathione, ascorbic acid, and heating inhibited the reaction strongly. 3. Comparative studies made on partially hepatectomized and normal rats substantiated the in vitro results. Partial hepatectomy caused rats to be more susceptible to the toxic effects of the drug and prolonged its pharmacologic action. Concomitantly higher tissue levels of d,l-methadone were obtained in most tissues, especially in the heart, lungs, spleen and kidneys.