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At least 19 recordsLinked to original sources
PubMed1989

Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage.

1. The pharmacokinetics of dextropropoxyphene (D) and nordextropropoxyphene (ND) have been studied in 12 healthy young (21-28 years) and 12 healthy elderly (70-79 years) male and female subjects. Each received 65 mg D and plasma D and ND concentrations were measured by h.p.l.c. with electrochemical detection for up to 7 days and again after 65 mg D, 3 times daily for 1 week. 2. There were no significant differences in median D and ND half-life, AUC, Cmax and tmax between the male and female subjects in either group. Within the groups the mean D half-life (h) was longer in the young after multiple dosing (mean +/- s.d.:13.2 +/- 5.2 and 23.7 +/- 11.3, P less than 0.05, paired t-test) but there were no other significant differences. 3. Between the groups, the median single and multiple dose D and ND half-lives were all significantly longer (P less than 0.02) and the median D AUC for both single and multiple doses was significantly higher (P less than 0.01 and P less than 0.05, respectively, Mann-Whitney U-tests) in the elderly. 4. There was no relation between multiple dose Cmax and other parameters such as single dose D half-life. However, across the groups D and ND half-lives after both single and multiple dosage correlated significantly with estimated creatinine clearance, the correlation being strongest with ND (r = -0.76 and -0.84, respectively).

Adult↗
PubMed1988

Psychomotor performance of patients with rheumatoid arthritis: cross-over comparison of dextropropoxyphene, dextropropoxyphene plus amitriptyline, indomethacin, and placebo.

Actions on performance of dextropropoxyphene (DXP) alone and in combination with amitriptyline (AMI), indomethacin (IN), and placebo were compared in 15 patients with rheumatoid arthritis. The patients were on their prescribed maintenance regimen excluding analgesics. In four randomized test sessions at two-week intervals, they received double blind and crossover single oral doses of DXP 130 mg, IN 50 mg, DXP 65 mg + AMI 25 mg or placebo, each after two days' pretreatment with the same drug. Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration. DXP impaired critical flicker discrimination, symbol copying and body balance without modifying tracking, choice reactions or attention. It rendered the subjects elated, muzzy, mentally slow and calm. Actions of AMI + DXP were about the same. IN impaired body balance and critical flicker recognition. Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low. We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills. Small doses of AMI may not enhance the mild psychomotor effects of DXP. Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance.

Adult↗
PubMed1984

Self-poisoning with dextropropoxyphene and dextropropoxyphene compounds: the USA experience.

This survey continues and expands earlier studies (Finkle et al., 1976a, b). A total of 27 medical examiner or coroner offices across the USA and Canada were visited. The combined jurisdictional population of these 27 sites is 64.8 million people: 56.5 million people in the USA (27% of the US population) and 8.3 million in Canada (Ontario). Since 1969 through mid-1983, a total of 4412 cases provided information sufficient for inclusion in this study. In each of the cases the presence of propoxyphene, and often its major metabolite, in the blood or tissues of the deceased was confirmed by toxicological analysis at the survey site. The following is a summary of the survey findings: The incidence of propoxyphene-associated deaths reached a peak in 1977, then declined by 22.2% from 1977 to 1978 and by 33.3% from 1978 to 1979, and by a further 10-18% since then. This continuing decline has occurred despite increased interest in propoxyphene misuse and the existence of improved analytical methods for the detection of propoxyphene and its metabolites. The decline is greater than can be accounted for by the decline in propoxyphene prescribing. The most common manner of death was suicide, accounting for about 45% of the cases; it can be safely assumed that the suicides were under-reported. A large majority of the suicides involving propoxyphene were multiple-drug intoxications, including alcohol. Propoxyphene alone was noted in about one-sixth of the suicides. These findings confirm those of the earlier studies, i.e., that a high proportion of the deaths associated with propoxyphene are suicides, and, in most cases, the deceased were victims of multiple-drug toxicity. More than 90% of cases involved persons between the ages of 20 and 40 years. There were very few instances of paediatric, adolescent or older adult deaths associated with propoxyphene. There is no evidence to support the view that the deceased were part of the street drug-abuse population. A history of heroin abuse appeared in less than 5% of the cases. Even fewer people had been known to have abused propoxyphene before their deaths, but 18% of the population had been known to 'self-medicate', using multiple drugs without appropriate medical supervision. The distribution of males to females approximated that of the US population.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed2000

Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain.

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Dextropropoxyphene is one example of an opioid analgesic in current use, and is widely prescribed for pain relief in combination with paracetamol under names such as Co-proxamol and Distalgesic. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single dose oral Dextropropoxyphene alone and in combination with paracetamol (acetaminophen) for moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from: Medline (1966 - November 1996), Biological Abstracts (1985 - 1996), Embase (1980 - 1996), the Cochrane Library (Issue 4 1996), and the Oxford Pain Relief Database (1954 - 1994). Additional studies were identified from the reference lists of retrieved reports. Date of the most recent searches: July 1998. SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included dextropropoxyphene and placebo or a combination of dextropropoxyphene plus paracetamol and placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Six trials (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. For a single dose of dextropropoxyphene 65 mg in postoperative pain the NNT for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 hours. For the equivalent dose of dextropropoxyphene combined with paracetamol 650 mg the NNT was 4.4 (3.5 to 5.6) when compared with placebo. These results were compared with those for other analgesics obtained from equivalent systematic reviews. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol compared with placebo. REVIEWER'S CONCLUSIONS: The combination of dextropropoxyphene 65 mg with paracetamol 650 mg shows similar efficacy to tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of adverse effects. The same dose of paracetamol combined with 60 mg codeine appears more effective but, with the slight overlap in the 95% confidence intervals, this conclusion is not robust. Adverse effects of both combinations were similar. Ibuprofen 400 mg has a lower (better) NNT than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.

Acetaminophen↗
PubMed1985

Effect of oral charcoal and urine pH on dextropropoxyphene pharmacokinetics.

The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of dextropropoxyphene were studied in six volunteers in a randomized, cross-over study. Serum and urine concentrations of dextropropoxyphene and norpropoxyphene were determined by GLC up to 72 h. Activated charcoal (50 g) given 5 min after dextropropoxyphene hydrochloride (130 mg), reduced its absorption by 97-99%. When given in repeated doses from 6 h on, 50 g followed by 12.5 g at 6 h intervals, charcoal significantly shortened the terminal serum half-life of dextropropoxyphene from 31.1 +/- 4.2 h to 21.2 +/- 3.1 h (p less than 0.05) and that of norpropoxyphene from 34.4 +/- 2.5 h to 19.8 +/- 3.4 h (p less than 0.001), and reduced their excretion into urine. The cumulative urinary excretion of unchanged dextropropoxyphene was increased 6-fold by acidification and reduced to 1/20 by alkalinization of urine, but the excretion of norpropoxyphene was much less dependent on urinary pH. However, the cumulative excretion of dextropropoxyphene and norpropoxyphene even into acidic urine accounted for less than 25% of the dose during 72 h. Because urinary pH has a great influence on the ratio of urinary versus serum dextropropoxyphene concentrations, pH should be taken into consideration, when the clinical significance of its concentration in urine is evaluated. Activated charcoal in high doses effectively prevents the absorption of that fraction of dextropropoxyphene which is in the stomach at the time of charcoal administration. Given in repeated oral doses, charcoal increases to some extent the rate of elimination of dextropropoxyphene and norpropoxyphene, probably by interrupting their enterohepatic or enteroenteric circulation.

Administration, Oral↗
PubMed1998

Single-dose dextropropoxyphene in post-operative pain: a quantitative systematic review.

OBJECTIVE: To determine the analgesic efficacy and adverse effects of single-dose oral dextropropoxyphene alone and in combination with paracetamol for moderate to severe post-operative pain. METHODS: Published reports were identified from a variety of electronic databases including MEDLINE, Biological Abstracts, EMBASE, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat for one patient to achieve at least 50% pain relief. Six reports (440 patients) compared dextropropoxyphene with placebo and five (963 patients) compared dextropropoxyphene plus paracetamol 650 mg with placebo. RESULTS: For a single dose of dextropropoxyphene 65 mg in post-operative pain the number-needed-to-treat for at least 50% pain relief was 7.7 (95% confidence interval 4.6 to 22) when compared with placebo over 4-6 h. For the equivalent dose of dextropropoxyphene in combination with paracetamol 650 mg the number-needed-to-treat was 4.4 (3.5 to 5.6) when compared with placebo. Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol when compared with placebo. A rank order of single-dose analgesic effectiveness in post-operative pain of moderate to severe intensity obtained from similar systematic reviews is presented. CONCLUSION: Dextropropoxyphene 65 mg plus paracetamol 650 mg has a similar analgesic efficacy to that of tramadol 100 mg but with a lower incidence of adverse effects. Ibuprofen 400 mg has a lower (better) number-needed-to-treat than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.

Acetaminophen↗
PubMed1980

Mild analgesics as an alternative to ergotamine in migraine. A comparative trial with acetylsalicylic acid, ergotamine tartrate, and a dextropropoxyphene compound.

The effect of ergotamine tartrate was compared with that of acetylsalicylic acid and a dextropropoxyphene compound (Doleron novum) on 525 acute migraine attacks in a double-blind crossover study of 25 adult female patients. Ergotamine tartrate and the dextropropoxyphene compound were equally effective and significantly superior to acetylsalicylic acid in preventing the attacks entirely. If the attacks were only partially prevented, the dextropropoxyphene compound was significantly superior to acetylsalicylic acid in making the attacks shorter and milder, while ergotamine tartrate did not differ significantly from acetylsalicylic acid or the dextropropoxyphene compound. The incidence of nausea and vomiting was lowest during treatment with the dextropropoxyphene compound. In the patients' overall preference, the dextropropoxyphene compound and ergotamine tartrate were significantly superior to acetyl-salicylic acid. In acute migraine the combination of dextropropoxyphene, a centrally acting analgesic, with acetylsalicylic acid and phenazone gives an alternative to ergotamine tartrate that is equally effective and causes less nausea and vomiting.

Adult↗
PubMed1997

The clinical relevance of the interaction between carbamazepine and dextropropoxyphene in elderly patients in Gothenburg, Sweden.

OBJECTIVES: To evaluate the clinical importance of the interaction between carbamazepine (CBZ) and dextropropoxyphene in elderly patients. METHODS: All patients (n = 7263) in Gothenburg, Sweden, who were part of a drug-dispensing programme, were included in the study. Eight per cent of the patients took CBZ and 18% took dextropropoxyphene, continuously. Patients who used a combination of these drugs were compared with patients who took only CBZ or dextropropoxyphene or neither of the two drugs. These four groups of patients were matched to each other with reference to gender, age and concomitant medication, which finally resulted in 21 patients in each group. A questionnaire with 30 symptoms of well-being, including symptoms typical of adverse effects of CBZ, were answered by the patients with the help of a registered nurse. Venous blood samples were drawn from the patients for the analysis of CBZ, its metabolite CBZ 10,11-epoxide (CBZ-E) and dextropropoxyphene. RESULTS: The doses of CBZ and dextropropoxyphene were lower among patients who used the combination of the two drugs than among those who only used one of the drugs. The mean level of CBZ in serum (S-CBZ) was, however, significantly higher and the level of CBZ-E in serum (S-CBZ-E) significantly lower among the patients who used the combination of CBZ and dextropropoxyphene, thus indicating an inhibition of the metabolism of CBZ. The prevalence of symptoms indicating side effects of CBZ was significantly higher in the group of patients who used both drugs. CONCLUSION: This study has shown that the combination of CBZ and dextropropoxyphene is hazardous in elderly patients and should be used with caution.

Aged↗
PubMed1979

Entrance into brain of dextropropoxyphene and the toxic metabolite norpropoxyphene.

Several studies show that dextropropoxyphene after oral administration is intensively biotransformed to norpropoxyphene by first pass metabolism in the liver. While dextropropoxyphene is analgesic, cardiotoxic and shows CNS toxicity with convulsions and respiratory depression, norpropoxyphene is cardiotoxic to the same degree as dextropropoxyphene, but is without analgesic or CNS-toxic effects (Lund-Jacobsen, 1978). This principal difference between the effects of dextropropoxyphene and norpropoxyphene might be due to differences in penetration into the brain. We investigated the penetration of the two compounds in 14C-labelled moities into the brain of rats by the technique originally described by Oldendorf (1970). By this method the extraction of dextropropoxyphene was found extremely high, while it was much lower for the metabolite. The extraction percentage for dextropropoxyphene after 5 and 10 S was 350 +/- 34.1 and 164 +/- 15.2, respectively, while the values for norpropoxyphene was 62 +/- 6.2 and 44 +/- 4.1 (mean +/- S.E.M.), respectively. This difference may at least partly explain the missing CNS-symptoms with the metabolite.

Animals↗
PubMed1990

Dose-response inhibition of rat compound nerve action potential by dextropropoxyphene and codeine compared to morphine and cocaine in vitro.

1. The effects of dextropropoxyphene hydrochloride (dextropropoxyphene) codeine phosphate (codeine), morphine hydrochloride (morphine), and cocaine hydrochloride (cocaine) on the compound action potentials (cAP) of the rat phrenic nerve were studied in vitro. 2. Dextropropoxyphene, cocaine, codeine and morphine depressed the cAP in a reversible, dose-dependent way. After 60 min exposure to the drugs, dextropropoxyphene, inhibited the cAP between 0.025 and 0.5 mM, cocaine between 0.01 and 5 mM, codeine between 0.1 and 10 mM and morphine between 0.5 and 70 mM. The inhibition caused by 5 mM morphine could not be reversed by naloxone. 3. Dextropropoxyphene demonstrated the most potent cAP inhibition compared to the other drugs tested. The observed dose range for the inhibition of the cAP of rat phrenic nerve includes that observed after intoxications with dextropropoxyphene (0.004-0.06 mM) in the clinic. 4. For all other drugs tested the present observed dose ranges are much greater than the plasma concentrations previously reported after therapeutic use and intoxication.

Action Potentials↗
PubMed1984

Deaths from paracetamol and dextropropoxyphene (Distalgesic) poisoning in England and Wales in 1979.

Paracetamol and dextropropoxyphene were implicated on clinical and analytical grounds in 237 poison deaths in England and Wales in 1979. In addition to paracetamol, dextropropoxyphene and ethanol, other agents were detected in 61 of these cases (26%). Analytical evidence suggests that very substantial overdoses of paracetamol and dextropropoxyphene were ingested in the majority of cases; their mean plasma concentrations in those ingesting no other agents were 252 and 8.64 mg/l respectively. Significant quantities of ethanol were ingested in 133 of 237 cases (56%). The mean ethanol concentration in those in whom quantitative estimations of paracetamol, dextropropoxyphene and ethanol were undertaken and who had not ingested other drugs, was 1588 mg/l. There was no analytical support for the diagnosis of paracetamol and dextropropoxyphene poisoning in 74 of 305 cases (24%) of H.M. Coroners' returns to the Office of Population, Censuses and Surveys for the period 1 January-31 December 1979. In addition, dextropropoxyphene was detected analytically in six cases classified as being due to paracetamol alone.

Acetaminophen↗
PubMed1985

Treatment of sports injuries with naproxen sodium and dextropropoxyphene napsylate.

Sixty-eight football players suffering from moderate to severe soft-tissue injuries were studies for up to 14 days. Treatment was either 550 mg naproxen sodium or 100 mg dextropropoxyphene napsylate initially and then 275 mg naproxen sodium or 100 mg dextropropoxyphene napsylate 4-times daily. Signs and symptoms were assessed daily on 4-point scales. The time taken for patients to return to training and be available for selection were recorded. The outcome of treatment of signs and symptoms was very similar for both groups, the only statistically significant difference detected being for the amount of swelling, which showed greater improvement in the naproxen sodium group on Days 2 to 6. Patients in the naproxen sodium group returned to training approximately 1 day sooner than those in the dextropropoxyphene napsylate group. The majority of patients in both treatment groups did not require treatment for 14 days. The duration of treatment in the naproxen sodium group, however, was shorter, with 59% stopping medication by Day 10, as compared to 33% in the dextropropoxyphene napsylate group (p=0.03). Nine patients in the naproxen sodium group and 6 in the dextropropoxyphene napsylate group reported side-effects, all gastro-intestinal in origin. One patient in the former group was withdrawn because of the reaction. There were three further withdrawals. One patient in the naproxen sodium group was referred for surgery, 1 patient in the dextropropoxyphene napsylate group was lost to follow-up and the final patient withdrew because of lack of efficacy. Both treatments were effective and well tolerated but the patients in the naproxen sodium group showed a more beneficial response.

Adolescent↗
PubMed1995

The cognitive and psychomotor effects of opioid analgesics. I. A randomized controlled trial of single doses of dextropropoxyphene, lorazepam and placebo in healthy subjects.

Twelve subjects (3 male) took part in a randomised double-blind four way crossover study designed to examine the cognitive and psychomotor effects of single doses of dextroproxyphene. On four study days one week apart each subject received each study product (i) dextropropoxyphene napsylate 100 mg, (ii) dextropropoxyphene napsylate 200 mg, (iii) lorazepam 2 mg and (iv) placebo. Performance measures were simple reaction time, choice reaction time, number vigilance, memory scanning, word recall (immediate and delayed), word recognition, picture recognition, critical flicker fusion threshold (CFFT) and visual analogue scales of alertness, calmness and contentment. Lorazepam had a marked effect on the range of tests used illustrating the sensitivity of the best battery. This was in contrast to the effects of dextropropoxyphene. A dose related effect in CFFT was detected, the 200 mg dose producing a significant decrease in CFFT throughout the testing period. Dextropropoxyphene also showed a tendency to improve scores on the verbal memory tasks. These data indicate that dextropropoxyphene in the usual doses does not produce significant impairment of cognitive and psychomotor function.

Adult↗
PubMed1998

Dextropropoxyphene acts as a noncompetitive N-methyl-D-aspartate antagonist.

In order to elucidate whether opioid analgesics available on the Scandinavian market also act as noncompetitive N-methyl-D-aspartate (NMDA) antagonists, a series of commercially available opioids were screened for their affinity in [3H](RS)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine ([3H]MK-801) binding assays and potential inhibitory actions on responses to NMDA in the rat cortical wedge preparation. Of the screened compounds (codeine, dextropropoxyphene, etorphine, fentanyl, and morphine), only dextropropoxyphene, with an IC50 value in [3H]MK-801 binding of 5 microM, was found to be active. Further characterization of the interaction of dextropropoxyphene with the NMDA response in the rat cortical wedge preparation illustrated the noncompetitive NMDA antagonist activity of dextropropoxyphene. Analysis of the dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 190 microM and a Hill slope of 0.8.

Analgesics, Opioid↗
PubMed1987

Poisoning with dextropropoxyphene in Denmark.

The sale of dextropropoxyphene is rising in Denmark, and the number of both fatal and non-fatal cases of poisoning with dextropropoxyphene is similarly rising. A total of 124 fatal and 297 non-fatal hospitalized cases of poisoning caused by dextropropoxyphene were reported to the National Board of Health in 1984. These figures are judged to be minimum figures. There is an accumulation of cases in the municipality of Copenhagen as compared to the remainder of the country. Cases of poisoning with dextropropoxyphene occur more frequently in socially and mentally encumbered groups. It is often difficult to determine with certainty the method of poisoning, but it is considered that the distribution is roughly one-third suicide or attempted suicide, about the same from accidental or simple over-dosage, while the remainder are uncertain. It is judged that the number of suicides or attempted suicides in normal persons is small, while the numbers in persons not entirely normal or carried out as an impulsive act are considerably higher. Other intoxicants, most frequently alcohol, have in more than one half of the cases been consumed together with dextropropoxyphene. The mortality rate for those cases reaching medical aid has been found to be 3.6% which is lower than the figure reported in other investigations. Very many of the cases of poisoning, however, are fatal at the time of discovery. Serious sequelae after non-fatal cases of poisoning are extremely rare. The steps being taken by the National Board of Health to reduce the number of cases of poisoning are mentioned, and the possibilities of reducing the number of cases are also discussed.

Adolescent↗
PubMed1992

Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites.

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.

Administration, Oral↗
PubMedDate not supplied

Dextropropoxyphene overdose. Epidemiology, clinical presentation and management.

This paper comprehensively reviews the worldwide situation regarding acute overdosage of dextropropoxyphene (propoxyphene). The changing epidemiology of this type of poisoning over the last 20 years is described with discussion of concurrent trends and, in particular, the effects of different preventive measures adopted in various countries. The clinical pharmacology of dextropropoxyphene relevant to the clinical toxic effects resulting from acute overdosage is described, and the management is detailed. In particular, the importance of early diagnosis and treatment is stressed in view of the potentially lethal complications that may suddenly occur with this poisoning. Recommendations for the correct use of the specific narcotic antagonist, naloxone, are made, together with other intensive supportive measures. As dextropropoxyphene is frequently taken together with other toxic agents, the concomitant effects of alcohol and sedative drugs are described and the treatment of paracetamol (acetaminophen) in combination with dextropropoxyphene is emphasised. The most effective preventive measures for the future are suggested, but caution is advised regarding the prescription for 'at risk' patients of alternative analgesics, which may be no safer in overdosage.

Dextropropoxyphene↗