Hilman W. Culp

The fate of radiocarbon-labeled propoxyphene in rat, dog, and human.

Abstract Propoxyphene N -demethylation is the primary initial metabolic step in the rat. Ester hydrolysis also occurs. A large number of metabolic end products of propoxyphene are formed. They are mainly excreted in bile as conjugates. Metabolism in the dog appears to be less complex than in the rat. Norpropoxyphene and one other metabolite predominate, although several minor metabolites are present. The human differs from the rat and dog in that propoxyphene metabolites are eliminated primarily in urine rather than bile. Only one major metabolite, unconjugated norpropoxyphene, is present. This is readily isolated and characterized as the alkaline rearrangement product norpropoxyphene amide. Norpropoxyphene concentrations in human plasma are higher than those of propoxyphene. The half-life of norpropoxyphene is also substantially longer than that of propoxyphene.

The metabolism of nortriptyline-N-methyl-14C in rats

Abstract Nortriptyline, labeled with radiocarbon in the N-methyl group, has been prepared and its metabolism, distribution, and excretion studied in the rat. About 25% of an administered dose undergoes N-demethylation in the whole animal. Another 40% of the dose is excreted in urine as conjugates of the cis and trans isomers of 10-hydroxy-nortriptyline. Distribution studies demonstrate that the drug undergoes wide distribution, with the highest levels found in lung and liver. Nortriptyline was identified in the brain, showing that it does pass the blood-brain barrier; it also was found to be slowly, but efficiently, absorbed from the intestinal tract.