Robert L. Wolen

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.

Concentration of propoxyphene in human plasma following oral, intramuscular, and intravenous administration

Abstract Propoxyphene hydrochloride was administered po, im, and iv to normal human volunteers. Included in the cross-over study were oral doses of propoxyphene napsylate equimolar with the oral doses of the hydrochloride salt. Concentrations of propoxyphene in the plasma of these subjects were determined periodically after each medication. Differences in plasma concentrations following the 2 salts were small in comparison with those among subjects and among doses. It was, therefore, concluded that these differences had little, if any, therapeutic importance. The biologic half-life following im medication was longer than that following po therapy; the half-life measurement after iv administration was much shorter than for the other 2 routes. The mean biologic half-life for propoxyphene administered iv was 1.85 hr.

Concentration of propoxyphene in human plasma following repeated oral doses

Abstract Propoxyphene hydrochloride was administered po to normal human volunteers. Included in the crossover study were po doses of propoxyphene napsylate equimolar with the doses of the hydrochloride salt. The concentrations of propoxyphene in the plasma of these subjects were determined periodically after each medication. The differences in plasma concentrations following these salts were small in comparison with those among subjects and among doses. It was, therefore, concluded that these differences had little, if any, therapeutic importance.

Adsorption of Propoxyphene Hydrochloride by Activated Charcoal

(1972). Adsorption of Propoxyphene Hydrochloride by Activated Charcoal. Clinical Toxicology: Vol. 5, No. 3, pp. 317-329.

Analgesia scores as timed responses following oral administration of propoxyphene to postpartum patients.

Abstract Two propoxyphene salts, the hydrochloride and the napsylate, were administered in equimolar quantities as single oral doses to women reporting postpartum uterine cramping. The double-blind doses included 32, 65, and 130 mg of the hydrochloride and 50, 100, and 200 mg of the napsylate salt. Identical-appearing placebo capsules were included. Grouping the patients according to the intensity of pain treated and assigning paired patients to different treatment groups was an important part of the procedure. The results (analgesia scores) indicate a linear dose-response over this range and no significant differences between the propoxyphene salts.

The concentration of propoxyphene in the plasma and analgesia scores in postpartum patients.

Abstract Equimolar quantities of 2 propoxyphene salts were administered as single oral doses to women reporting postpartum uterine cramping. The doses included 32, 65, and 130 mg of the hydrochloride and 50, 100, and 200 mg of the napsylate salt. Identical-appearing placebo capsules were included. Both analgesia scores and plasma concentrations were determined. The correlation between these 2 measures of response was not significant when all of the 336 pairs of individual observations were included in the computation. Both responses were related to amount of drug ingested, and on this basis the means of the analgesia scores and the concentrations in the plasma were significantly correlated.

Tracer microspheres as compliance markers in clinical research

Tracer microspheres are small, ceramic-like particles (50 micron) containing one of several radionuclide markers. We have utilized them over a period of 9 years as quantitative fecal markers for recovery measurements in metabolic studies. The markers have been administered daily for up to 2 weeks, during which time the marker concentration per unit dry weight of feces remains fairly constant. Data on the markers and our experience with them are presented along with the concerns that must be addressed in considering them as compliance markers.