Printed in U.S.A. STOP-FLOW ANALYSIS OF THE RENAL EXCRETION OF TRITIUM-LABELED DIHYDROMORPHINE’2

The kidney is the major organ for excretion of the opiate drugs and their metabolites (Way and Adler, 1960, 1962) , but the manner in which these compounds are handled by the kidney has received little attention. Data ob-tamed by Ozawa (1930) and by Baker and Woods (1957) suggest the possibility of active tubular excretion of morphine in addition to glomerular filtration of the drug. The present study was undertaken to clarify the role of the renal tubule in the urinary excretion of mor-phine-like analgesics. For this investigation tritium-labeled dlihy-dromorphine (DHM-W) was administered to nontolerant dogs and monkeys and to morphine-tolerant monkeys. The mode of the renal excre-tion of free and of conjugated DHM-H3 was analyzed by the stop-flow method of Malvin et at. (1958). DHM-H3 was employed because this compound was easily synthesized with high specific radioactivity. The qualitative similarity to morphine in pharmacologic action, biologic fate, and physical properties (Hug and Mellett, 1963, 1965) makes it likely that the renal excre-tion of DHM-H3 is at least qualitatively similar to that of morphine. METHODS. Synthesis. Tritium-labeled dihydro-morphine (DHM-H8) was synthesized by catalytic Received for publication February 22, 1965