STOP-FLOW ANALYSIS OF THE RENAL EXCRETION OF TRITIUM-LABELED DIHYDROMORPHINE

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Active secretion of free and conjugated tritium-labeled dihydromorphine (DHM-H³) by the proximal portion of the renal tubules of dogs and monkeys was demonstrated with the stop-flow method. Mepiperphenidol reduced in vivo secretion and in vitro tissue slice accumulation of free DHM-H³. Both mepiperphenidol and probenecid decreased the in vivo secretion of conjugated DHM-H³, which is presumed to contain an acidic moiety (glucuronic acid) as well as a basic (piperidine nitrogen) group. Nonionic diffusion appeared to be minimal for free DHM-H³ in these experiments, but lower U/P ratios for conjugated DHM-H³ could be correlated with decreasing urinary pH. Stop-flow patterns did not demonstrate an area of net reabsorption of either free or conjugated DHM-H³. Monkeys exhibiting high-grade physical dependence and tolerance to morphine were found not to differ from nontolerant monkeys in their tubular secretion of DHM-H³. Nalorphine in concentrations approximately equal to those of DHM-H³ did not alter renal secretion in vivo in a consistent manner, or tissue uptake in vitro to a biologically significant extent.

Dogs appeared to secrete free and conjugated DHM-H³ more efficiently than did monkeys, although the reverse was true for p-aminohippurate.

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