Charles M. Gruber

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.

The effectiveness and side-effect liability of propoxyphene hydrochloride and propoxyphene napsylate in patients with postpartum uterine cramping.

Abstract A balanced Latin square design was used to evaluate the effectiveness and acceptability of 2 propoxyphene salts in consenting postpartum patients with pain. Attention was paid to the intensity of pain and its change on treatment, an estimate of pain relief, and the frequency and intensity of symptoms other than pain. Analgesia scores were calculated from change in pain intensity and estimate of relief. The initial pain intensity had a significant linear relationship to the analgesia score, to the onset and duration of analgesia, and to the number and intensity of other symptoms. Greater analgesia and an earlier onset were observed with propoxyphene than with the blank control. The response to propoxyphene (as measured by the onset and duration of analgesia and the frequency and intensity of other symptoms) was linear to the log dose. The napsylate salt had a significantly longer duration of action, which may account for its apparently greater potency. Other symptoms were reported less frequently and were of a lower intensity after the napsylate than after the hydrochloride salt.

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.

A comparative study of the effects of chronic administration of propoxyphene salts to normal volunteers

Abstract Two salts of the oral analgesic agent propoxyphene, the hydrochloride salt and the 2-naphthylene sulfonic acid salt, were evaluated for safety in a 6-month study in normal male inmates of a penal institution. Parameters measured included subjective side effects, hematologic response, blood chemistry, and urine analysis as well as routine physical examination. There were 40 subjects in each drug group initially, and a concomitant control group of 40 subjects received placebo capsules for the duration of the study. There were no changes in any of the parameters measured which could be attributed to the drugs. An epidemic of mild, anicteric hepatitis did produce changes in liver function as measured by serum transaminases and alkaline phosphatase levels; however, these occurred with equal frequency in all 3 groups and were also observed in subjects not participating in the study. The results indicate the value of concomittant placebo controls in a study of this type.

Relief of postpartum uterine cramping with propoxyphene and aspirin

Abstract Two propoxyphene salts, the hydrochloride and the napsylate, were administered in equimolar quantities as capsules to women professing postpartum uterine cramping. The doses used were 65 and 130 mg of the hydrochloride and 100 and 200 mg of the napsylate. Enteric-coated aspirin tablets, in doses of 325 and 650 mg, were also included in the study, as were identical-appearing placebo capsules and tablets. Single oral doses consisting of 1 capsule and 2 tablets were given with the double-blind control so that equal numbers of patients were treated with each of the 15 medication combinations. Responses in proportion to the dose followed the administration of propoxyphene and of aspirin. Large doses of both analgesics in combination were associated with responses less than expected from the sums of the responses to these same doses given separately. This phenomenon may result from a plateau effect associated with maximum response. A relationship between dosage and possible side effects was not demonstrated.