Abstract

The influence of some pituitary and adrenocortical hormones on the absorption and metabolism of methadone-2-C¹⁴ by rats has been investigated using tracer and countercurrent distribution techniques. Cortisone treatment enhanced absorption but apparently not by virtue of an antihistaminic action. Of several treatments which depressed absorption, the most marked decrease was seen after vasopressin administration. Tissue distribution of carbon-14 was most affected by cortisone or its absence. Thus, brain and spinal cord levels were low in cortisone- or ACTH-treated rats and in adrenalectomized rats maintained on cortisone but were high in adrenalectomized rats maintained on NaCl. Concomitantly, intestinal carbon-14 levels indicated more rapid excretion after cortisone treatment and the opposite in adrenalectomized rats maintained on NaCl. Brain and spinal cord levels were not altered in histamine-depleted, antihistamine- or vasopressin-treated rats but excretion as well as absorption was slowed by the two latter treatments. Muscle and liver carbon-14 levels were similar in all cases and no marked shift in urinary excretion was noted. Countercurrent distribution studies of bile from control, cortisone-treated and adrenalectomized rats indicated the presence of methadone and two metabolites in all groups but no qualitative or quantitative differences in metabolism. However, liver slices from adrenalectomized rats after incubation with methadone contained less methadone and metabolites than slices from control or cortisone-treated rats. It is concluded that the anti-inflammatory actions of cortisone are related to these observations and that an antihistaminic action is not involved.