SEARCH · PubMed Health

Results for “PROPOXYPHENE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1975

Propoxyphene and norpropoxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate.

Propoxyphene and its major metabolite norpropoxyphene have been determined in blood and liver in 29 cases of death in which propoxyphene, either as the hydrochloride or as the napsylate salt, was involved. The use of propoxyphene napsylate (Darvon-N) contributed to the deaths of 4 persons, 3 of whom were former heroin addicts receiving large amounts of this drug in connection with propoxyphene substitution programs. In the majority of cases the norpropoxyphene blood concentrations exceed the propoxyphene concentrations, although brain determinations in several instances indicate that norpropoxyphene does not cross the blood-brain barrier with the same ease as propoxyphene. On the basis of the comparative toxicities of propoxyphene and norpropoxyphene in animals and the high tissue concentrations of norporpoxyphene in man after propoxyphene administration, it is conceivable that norpropoxyphene contributes to the toxic effects of propoxyphene.

Adult↗

PubMed1976

Effect of l-propoxyphene on plasma levels and analgesic activity of d-propoxyphene in the rat.

Oral administration of l-propoxyphene with d-propoxyphene enhances the analgesic activity of d-propoxyphene as expressed in the rat tail heat test. The combination of d- and l-propoxyphene at a dose of 10 mg/kg each was found to have activity in the analgesic assay equivalent to that observed with d-propoxyphene at a dose of 20 mg/kg. In the same test, l-propoxyphene at a dose of 40 mg/kg had no activity. Co-administration of equal amounts of l-propoxyphene with d-propoxyphene (10 mg/kg p.o.) results in an increase in circulating plasma levels of d-propoxyphene from 9 +/- 2 to 114 +/- 39 ng/ml 15 minutes after administration. The increase in plasma levels is accompanied by a proportional increase in the brain and lung levels with no significant change in the liver levels. When d-propoxyphene (4 mug/ml) was infused in the isolated perfused rat liver, over 98% of the drug was extracted in a single pass through the liver. When l-propoxyphene was added to the perfusate (4 mug/ml), the extraction of d-propoxyphene was decreased to less than 90%. These results indicate that l-propoxyphene increases the systemic availability of d-propoxyphene by altering the amount of d-propoxyphene extracted by the liver.

Administration, Oral↗

PubMedDate not supplied

Serum propoxyphene concentrations in a cohort of opiate addicts on long-term propoxyphene maintenance therapy. Evidence for drug tolerance in humans.

Propoxyphene, norpropoxyphene, and cyclic dinorpropoxyphene concentrations in the sera of eight opiate addicts were measured by gas chromatography. The addicts were enrolled in a propoxyphene maintenance program and had received 800-1600 mg of propoxyphene napsylate daily for 13-50 months. Serum propoxyphene and norpropoxyphene ranged from 127 to 1070 ng/mL and 814 to 2638 ng/mL, respectively, and their ratio ranged from 0.1 to 0.4. A roughly linear dose-to-serum-concentration relationship was found for serum propoxyphene and norpropoxyphene in the cohort. Cyclic dinorpropoxyphene was detected in three of the subjects' sera. Because tolerance to propoxyphene occurs, knowledge of prior drug exposure is necessary to determine whether an elevated propoxyphene or norpropoxyphene concentration is toxic to patients or decedents with apparent propoxyphene overdose. Serum norpropoxyphene concentration exceeds that of propoxyphene following chronic propoxyphene use. Measurable cyclic dinorpropoxyphene implies chronic propoxyphene use but its absence does not exclude chronic use.

Adult↗

PubMed1976

Simultaneous estimation of propoxyphene-do and propoxyphene-d2 levels by quantitative mass fragmentography. Potential utility in multidose investigations.

A quantitative mass fragmentographic method for the simultaneous determination of labeled and unlabeled propoxyphene in plasma is described. Dogs treated daily with propoxyphene-do were treated with a pulse dose of propoxyphene-d2 at day 20. It was found that following an initial rapid equilibrium phase levels of propoxyphene-d2 fell more rapidly than those of propoxyphene-do. This result suggests that 'deep' pools of tissue bound propoxyphene exist which exchange very slowly with drug present in the central compartment. Experimental evidence is presented which demonstrates that the difference in behavior of propoxyphene-do and -d2 is not due to unanticipated secondary isotope effects.

Administration, Oral↗

PubMed1980

Propoxyphene and norpropoxyphene plasma concentrations after oral propoxyphene in cirrhotic patients with and without surgically constructed portacaval shunt.

Plasma concentrations of propoxyphene and its major metabolite, norpropoxyphene, were determined over at least 12 hr after oral administration of 130 mg dextropropoxyphene hydrochloride to eight men with hepatic cirrhosis, of whom four had a surgically constructed portacaval shunt, and to seven healthy men. Propoxphene concentrations were appreciably higher and norpropoxyphene concentrations were much lower in the patients than in the normal subjects. The ratio of areas under the plasma concentration-time curve from 0 to 12 hr, norpropoxyphene: propoxyphene, was 0.70 +/- 0.46 (x +/SD) in patients and 3.94 +/ 0.83 in normal subjects. A similar decrease in this ratio was observed previously in otherwise healthy dogs after surgical construction of portacaval shunt when propoxyphene was given orally, but not after intravenous injection of the drug. A woman with portacaval shunt and essentially complete renal failure was also studied; she exhibited the highest propoxyphene peak concentration in this investigation and had no detectable norpropoxyphene in plasma. Most of the patients, unlike the normal subjects, experienced considerable sedation after propoxyphene. These results are probably due to increase systemic availability of orally administered propoxyphene in patients with hepatic cirrhosis and possibly to increased receptor response to the drug by these patients. It is concluded that propoxyphene should be administered cautiously and in reduced doses to patients with hepatic dysfunction.

Adult↗

PubMedDate not supplied

Synthesis of new d-propoxyphene derivatives and the development of a microparticle-based immunoassay for the detection of propoxyphene and norpropoxyphene.

The synthesis of [S-(R,S)]-4-[[methyl[2-methyl-3-(1-oxopropoxy)-3, 4-diphenylbutyl]amino]-1-oxobutoxy]-2,5-pyrrolidinedione+ ++ (propoxyphene active ester, 2) is described. This was used as an intermediate to prepare a propoxyphene immunogen, [S-(R,S)]-4-[methyl][2-methyl-3-(1-oxopropoxy)-3,4-diphenylbuty l]-amino]- 1-oxobutyl-Bovine Thyroglobulin (3). This immunogen was then used to generate antibodies which demonstrate good cross-reactivity to d-propoxyphene, d-norpropoxyphene, and other propoxyphene metabolites. In addition, these antibodies were shown to have very low cross-reactivity to methadone, a structurally related compound. The introduction of an aminomethyl benzoate spacer into the propoxyphene active ester (2), followed by the activation of the carboxylic acid, provided for a more stable active ester (5). This stable active ester, together with the antibodies generated from the propoxyphene immunogen, has led to the development of an immunoassay based on the Kinetic Interaction of Microparticles in Solution (KIMS).

Animals↗

PubMed1994

D-propoxyphene and norpropoxyphene kinetics after the oral administration of D-propoxyphene: a new approach to liver function?

In an attempt to design a liver function test which takes into account both portal-systemic shunting and hepatocellular dysfunction, we investigated a group of patients with cirrhosis with or without surgical porta-caval shunt for d-propoxyphene and its major metabolite, norpropoxyphene kinetics. A small dose of d-propoxyphene (0.7 mg/kg body weight) was given orally to seven normal subjects, 15 patients with cirrhosis and seven patients with cirrhosis and surgical portacaval shunt. D-propoxyphene and norpropoxyphene areas under the plasma concentration-time from 0 to 4-h (AUC) were determined by the trapezoidal method. As d-propoxyphene is a high extraction drug and since the production of norpropoxyphene should reflect the amount of d-propoxyphene available to the hepatocytes, we tested the hypothesis that norpropoxyphene/d-propoxyphene AUC ratios should reflect both the degree of portal-systemic shunting and the severity of hepatocyte dysfunction. Norpropoxyphene/d-propoxyphene AUC ratios were significantly lower in patients with cirrhosis (mean +/- S.D.: 0.92 +/- 0.59) than in controls (2.51 +/- 0.45) and also significantly lower in patients with cirrhosis and a surgical shunt (0.53 +/- 0.23) than in patients with cirrhosis but without surgical shunt (1.10 +/- 0.63). Moreover, there was an overall statistically significant correlation between norpropoxyphene/d-propoxyphene AUC ratios and branched to aromatic amino acids ratios (rs = 0.91) and fasting venous NH4 (rs = -0.63). On the other hand, there was only a weak correlation between norpropoxyphene/d-propoxyphene AUC ratios and the 14C-aminopyrine breath test (rs = 0.43). These data suggest that the norpropoxyphene/d-propoxyphene AUC ratio reflects both shunting and reduced hepatocellular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1976

Simultaneous measurement of plasma levels of d-Propoxyphene and l-Propoxyphene using stable isotope labels and mass fragmentography.

When racemic propoxyphene was administered orally to dogs, plasma levels of d-propoxyphene were higher than those of l-propoxyphene. The half-life of d-propoxyphene was also longer than that of the l-isomer. Measurements were performed by labeling one isomer of a racemic mixture with deuterium and then measuring d- vs. l- ratios by mass fragmentography. An intravenous experiment was also performed and confirmed the preferential uptake of the levo isomer. To do these experiments successfully propoxyphene isomers were labeled on the benzyl methylene with deuterium atoms. In vivo studies demonstrated that this labeling position was sufficiently far removed from the point of metabolic attack in the molecule so that no interfering isotope effect existed. The methodology outlined in this paper will be of great value in the study of the disposition of the individual isomers of racemic drugs.

Animals↗

PubMedDate not supplied

A comparative analgesic study of propoxyphene, fenoprofen, the combination of propoxyphene and fenoprofen, aspirin, and placebo.

Groups of 27 inpatients with moderate or severe postoperative, fracture, or somatic pain were given single oral doses of propoxyphene napsylate (P), fenoprofen calcium (F), combinations of P and F, aspirin, or placebo. The increasing rank order for effectiveness, with doses in milligrams, was placebo, P50, aspirin 650, F600, F50, P50 + F50, F200, P50 + F600, P50 + F200, P200 + F50, P200, P200 + F200, and P200 + F600. The overall analgesic response to propoxyphene in this dose range (50 to 200 mg) increased linearly with increasing doses. The fenoprofen response also increased in proportion to the dose up to 200 mg; the overall response to 600 mg was not significantly different from that to 200 mg. Propoxyphene napsylate and fenoprofen calcium had additive analgesic effects. There were no drug-related adverse reports.

Aspirin↗

PubMed1986

Severe acute propoxyphene overdose: plasma concentrations of propoxyphene and norpropoxyphene and the effect of dopamine on circulatory failure.

Twelve patients with cardiovascular failure because of propoxyphene self-poisoning were treated with dopamine. The patients responded favourably to dopamine infusion (2-17 micrograms/kg/min) with a dose-dependent rise in systolic arterial blood pressure and a fall in central venous pressure and copious urinary output. Side effects during infusion were few, and in periods where dopamine infusion exceeded 10 micrograms/kg/min no tachyarrhythmias were seen. Eleven of the patients were treated on a respirator. Two patients were discharged from the ICU with signs of hypoxic brain damage, one of whom recovered completely after 2 weeks. Serum propoxyphene and norpropoxyphene were measured in nine patients. All but one patient had either propoxyphene or norpropoxyphene concentrations above 3 mumol/l.

Adult↗

PubMed1975

Quantitation of propoxyphene and its major metabolites in heroin addict plasma after large dose administration of propoxyphene napsylate.

A sensitive and specific GLC assay method was developed for the determination of propoxyphene, its major metabolite norpropoxyphene, and lesser known metabolites cyclic dinorpropoxyphene and/or dinorpropoxyphene in plasma of heroin addicts administered up to 800 mg of propoxyphene napsylate. The assay used a mass internal standard of pyrroliphene. The compounds were extracted from pH 9.8 carbonate-buffered plasma with butyl chloride, back-extracted into acidified water which was then washed with hexane, and reextracted with chloroform from the aqueous phase made basic. Quantitation of the drug and its metabolites was accomplished by temperature-programmed GLC. Absolute identification of the compounds chromatographed was completed by GLC-mass spectrometry.

Chromatography, Gas↗

PubMed1982

Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene.

Plasma concentrations of propoxyphene (P) and its pharmacologically active metabolite norpropoxyphene (NP) were determined in normal subjects after single 130-mg oral doses and during and after 13 consecutive oral doses of 130 mg P, and in former heroin addicts who were maintained on 900 to 1200 mg of P per day. The data were analyzed using a first-pass elimination pharmacokinetic model. Both P and NP cumulated during repeated dosing to levels 5 to 7 times those after the first dose. In contrast, "maintenance" patients exhibited steady-state trough plasma NP cumulation that exceeded that of P by a factor of 13. Several changes in P and NP kinetics occurred during repeated dosing with P to the normal subjects: P clearance decreased from 994 to 508 ml/min, NP clearance decreased from 454 to 2210 ml/min, P half-life (t 1/2) increased from 3.3 to 11.8 hr, NP t 1/2 increased from 6.1 to 39.2 hr, and area under the concentration time curves for P and NP were doubled. These changes in kinetics during repeated dosing resulted in more extensive cumulation of P and NP than would be predicted from the single-dose kinetic profile. Changes in the extent of first-pass elimination of P result in variability in plasma P and NP that may contribute to P-induced toxicity.

Adult↗

PubMed1964