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At least 19 recordsLinked to original sources

PubMed1998

Determination and pharmacokinetics of dextromoramide in methadone maintenance therapy.

To study the pharmacokinetics of dextromoramide in long-term opiate addicts on methadone maintenance therapy (MMT) a reverse-phase HPLC technique was developed to monitor dextromoramide and methadone concentrations in plasma simultaneously. After liquid-liquid extraction from plasma, dextromoramide and methadone were determined using a Supelcosil LC-ABZ column and a mobile phase of KH2 phosphate buffer (25 mM, pH 2.5) mixed with acetonitrile (80:20, v/v) and UV detection at 206 nm. The method was found to be sufficiently sensitive, specific and reproducible to apply in six subjects on MMT for many years, receiving orally administered dextromoramide as adjuvant. Pharmacokinetic data sets for dextromoramide in each subject were conducted and analysed further, indicating short elimination half-life values (71 min, range 31-152 min). Contrary to previous studies, in all subjects tested the pharmacokinetics of dextromoramide are best described using an one-compartment model.

Adult↗

PubMed1989

[Pharmacokinetics of dextromoramide in the surgical patient].

The pharmacokinetics of dextromoramide were studied in nine patients undergoing peripheral vascular surgery. All the patients were anaesthetised with thiopentone and vecuronium. After tracheal intubation, anaesthesia was maintained with 0.5 to 1.5 vol % halothane and a 60%-40% vol nitrous oxide-oxygen mixture. Once the patient's status was stable, a 0.8 mg.kg-1 bolus of dextromoramide was given intravenously. Blood samples were obtained 2, 5, 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min afterwards by an arterial catheter. Dextromoramide serum concentrations were measured with high performance liquid chromatography after extraction with an original technique. The pharmacokinetic parameters were calculated by computer using TRIOMPHE. In five patients, a bi-exponential equation best fitted the results, whereas a tri-exponential equation was necessary for the other four. Mean elimination half-life was 215.3 +/- 78.4 min, and the apparent final volume of distribution was 0.58 +/- 0.20 l.kg-1. Hepatic extraction was low, as shown by a mean systemic clearance of 2.0 +/- 0.9 ml.kg-1.min-1. Liposolubility of this drug is the highest of all opiates, with a heptane/water partition coefficient of 12.3. These parameters demonstrate that, in the opiate drug group, dextromoramide has a place apart from the others.

Aged↗

PubMedDate not supplied

Determination of dextromoramide by capillary gas chromatography and electron impact mass spectrometry.

A sensitive and specific quantitative assay for the determination of dextromoramide in human fluids and tissues is described. Dextromoramide and an internal standard, SKF 525 A, are isolated by a basic extraction and back-extraction process. The final extract is separated on a 25-m capillary column B.P. 1 and drugs are detected by selected ion monitoring at m/z 100 and m/z 86 for dextromoramide and the internal standard, respectively. The minimum detectable quantities are 0.5 and 0.3 ng/mL, for dextromoramide in plasma and urine, respectively. Coefficients of variation for within-run data were less than 6%.

Dextromoramide↗

PubMed2004

Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain.

OBJECTIVE: To compare three opioid agonist drugs for perioperative analgesia in cats. STUDY DESIGN: Prospective, blind, controlled, randomised trial. ANIMALS: Ninety client-owned cats, weighing 3.1 (2.1-4.5) kg, aged 14.6 (6.0-84.0) months, were studied. METHODS: Seventy-six cats, scheduled for ovariectomy, received either 0.6 mg kg(-1) racemic methadone, 0.3 mg kg(-1) levo-methadone, 0.05 mg kg(-1) dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single 'blinded' observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Fe'CO2 and SpO2 were recorded during anaesthesia. Post-operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time-dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time-dependent variables were analysed using chi2-tests. Significance was set at p < or = 0.05. RESULTS: There were no significant changes in appearance after pre-anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals' reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate-to-severe pain after surgery. In the levo-methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, 'rescue' analgesia was required more often in cats treated with dextromoramide or saline. CONCLUSION AND CLINICAL RELEVANCE: Dextromoramide (0.05 mg kg(-1)) was ineffective, while racemic methadone (0.6 mg kg(-1)) and levo-methadone (0.3 mg kg(-1)) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.

Analgesics, Opioid↗

PubMedDate not supplied

Craving patterns in methadone maintenance treatment with dextromoramide as adjuvant.

A study was performed to establish the effect on opiate craving among six long-term opiate-dependent subjects in methadone maintenance treatment. Subjects currently stabilised on methadone, received 5 or 10 mg dextromoramide besides methadone. During the study the usual methadone dose was diminished according to the individual subject's expectation of the effect of dextromoramide addition. A clear drug-effect relationship between the increment of dextromoramide plasma concentration and decrement of opiate craving could be seen. A craving increase before drug administration was seen in three cases. The results could imply beneficial effects of a short-acting opiate on diminishing craving in opiate addicts who are difficult to stabilise with methadone maintenance treatment.

Adult↗

PubMed1989

[Chromatographic identification and analysis of dextromoramide in the plasma by the method of high performance liquid chromatography].

Dextromoramide and pethidine were separated and identified by thin-layer chromatography on silica gel, using ammonia and methanol (1.5:100) as the mobile phase, after previous extraction with dicthyl ether or with a mixture of n-hexane and isoamyl alcohol (98.5:1.5) from blood alkalized to pH 10.3 Dextromoramide can be revealed on the chromatograms in the amount of 0.5 micrograms and pethidine in the amount of 1 micrograms using the Dragendorff reagent. Reversed-phase TLC proved less sensitive. High-performance liquid chromatography on the column of LiChrosorb RP-18 was applied to the determination of dextromoramide in blood after extraction with diethyl ether, using methanol--phosphate buffer pH 4.5 (95:5) as the mobile phase. The determination range was of 0.5-5.0 micrograms per 2 cm3 of blood plasma (1.26.10(-8)-1.26.10(-7) mole/dm3).

Chromatography, High Pressure Liquid↗

PubMed1990

Teratogenic potential of two neurotropic drugs, haloperidol and dextromoramide, tested on mouse embryos.

Potential teratogenic activity of two neurotropic drugs, haloperidol and dextromoramide tartrate, was tested by using the mouse embryo experimental model. Like numerous other drugs of this class these two are also embryotoxic. After treatment 1 hour into the 9th gestation day they induce the neurotropic syndrome of malformations comprising exencephaly, craniorachischisis, kinking of the spinal cord, brachyury, and dilation of the fourth brain ventricle. In addition, dextromoramide tartrate was found to induce one more, so far unknown, neural tube defect, namely the ectopia of the neural tube. Delay of treatment by 1 or 2 hours tends to displace the location of the neural tube defects along the length of the neural axis towards the anterior and posterior directions. Even after accumulating these results at relatively high doses, it is difficult to estimate human reproductive risks from this animal data for human therapeutic doses.

Animals↗

PubMed1995

Characterization of dextromoramide (Palfium) abuse by hair analysis in a denied case.

By providing information on exposure to drugs over time, hair analysis is useful in verifying the history of drug use. In a clinical case, where drug abuse was denied, it was possible to identify dextromoramide in the hair of the subject. After acid hydrolysis of the hair with 0.1 M HCl, in the presence of SKF 525A as an internal standard, the drug was extracted at pH 8.4 with chloroform-isopropanol-n-heptane (50:17:33 v/v) and quantified by gas chromatography/mass spectrometry. The hair strands were cut into 3 sections of 2.5 cm, corresponding to a growth period of 2 months. Concentrations were 1.09, 1.93 and 1.48 ng/mg from the root to the end, respectively. This is the first report on dextromoramide testing in human hair.

Dextromoramide↗

PubMed1992

Determination of dextromoramide in plasma and whole blood using high-performance liquid chromatography with ultraviolet absorbance detection.

Dextromoramide was determined in plasma and whole blood after solid-phase isolation by high-performance liquid chromatography using dextropropoxyphene as internal standard and ultraviolet detection at 215 nm. Owing to its good selectivity, sensitivity and reproducibility, the technique is available for forensic toxicology purposes as well as for clinical pharmacology. The concentrations of dextromoramide were determined in three cancer patients receiving intravenous treatment with one to three 5-mg daily doses. On the fourth day the plasma level was 13.85 +/- 3.27 ng ml-1 just before the first daily dose and 84.28 +/- 12.60 ng ml-1 30 min after dosing. The whole blood concentration, determined in one of the patients, was undetectable just before the dose and was 76 ng ml-1 30 min after dosing.

Chromatography, High Pressure Liquid↗

PubMed1993

Simultaneous determination of dextromoramide, propoxyphene and norpropoxyphene in necropsic whole blood by liquid chromatography.

Dextromoramide, propoxyphene and its main metabolite, norpropoxyphene, were determined in blood after solid-liquid extraction by means of an HPLC method using photodiode-array detection. Two cases of fatal overdose resulting from abuse of the two drugs are presented. In case 1 the necropsic whole blood contained dextromoramide at toxic level (194 ng ml-1) and propoxyphene (614 ng ml-1) and norpropoxyphene (1100 ng ml-1) within the therapeutic range; the death could be due to the combined effect of the two analgesics and, perhaps, other associated drugs. In case 2, the necropsic whole blood concentrations of propoxyphene and norpropoxyphene were 4330 and 3800 ng ml-1, respectively, and could be considered as lethal.

Adult↗

PubMed1990

Gas chromatographic mass-specific investigation of dextromoramide (Palfium) metabolism in the horse.

Dextromoramide (Palfium) was given by intravenous injection to a Thoroughbred horse at a dosage of 20 mg and urine was collected 2, 4, 6 and 8 h after drug administration. Enzymatic hydrolysis of the urine followed by solvent extraction gave a residue which was back-extracted into 0.1 M sulphuric acid. After basification to pH 9 and solvent extraction, the resulting residue was submitted to gas chromatographic-mass spectrometric analysis. Both electron-impact and ammonia chemical-ionization mass spectra were recorded and, based on the observed fragmentation patterns, the principal metabolites in horse urine were shown to be 2,2-diphenyl-3-methyl-4-morpholinobutyramide (compound 2) and the product of hydroxylation of one phenyl ring in dextromoramide (compound 3), respectively. The electron-impact mass spectra of compounds 2 and 3, and of their derivatisation products from oncolumn methylation in the gas chromatograph, are reported.

Animals↗

PubMedDate not supplied

Fatal intoxication by dextromoramide: a report on two cases.

Two cases involving an overdose resulting from the abuse of dextromoramide are presented. The drug was quantified with a gas chromatograph equipped with a nitrogen phosphorous detector (NPD). The whole blood dextromoramide concentrations were 984.3 ng/mL for case 1 and 871.1 ng/mL for case 2. No correlations could be established with the postmortem levels in blood and in bile.

Adult↗

PubMed1989

Pharmacokinetics of dextromoramide in surgical patients.

The pharmacokinetics of the narcotic analgesic dextromoramide was investigated by means of a specific GC-MS method in 9 patients who were given a single oral dose of the drug (7.5 mg) together with an anticholinergic before undergoing minor orthopedic surgery. Dextromoramide was rapidly absorbed from the gastrointestinal tract, with peak plasma levels between 68 and 177 micrograms/L usually achieved within 0.5-4.0 h after dosing. In 5 patients, the decline of plasma concentrations after the peak followed a biphasic pattern, with half-lives of 0.4-1.6 h for the first phase and 6.3-21.8 h for the terminal phase. In the remaining patients, no clear-cut biphasic pattern was seen and half-lives calculated over the period between 4 h and 10 h after administration ranged from 1.5 to 4.7 h. Apparent clearance and volume of distribution values ranged from 0.06 to 0.36 1.h-1.kg-1 and from 0.6 to 2.4 l.kg-1, respectively. Less than 0.06% of the dose was excreted unchanged in urine within 8 h of administration. The concentration of the drug in a CSF sample collected 1 h after dosing was below the limit of detection (2 micrograms/L) in all subjects.

Adolescent↗

PubMed1990

Tissue distribution of dextromoramide in the rat.

The tissue distribution of dextromoramide was studied in rats after the intraperitoneal injection of 0.2 mg/kg of the drug. The pattern of distribution was similar at 15, 30, 60 and 90 min, with the highest concentrations being found in the liver and the myocardium, while other organs were not able to concentrate dextromoramide.

Animals↗

PubMed1990

A dextromoramide-related fatality.

A 38-year-old man was found in his car suffering from a heart attack. Serum analysis by capillary gas chromatography and mass spectrometry confirmed the presence of dextromoramide (Palfium), methadone, and lidocaine. The serum concentrations at admission to the hospital were: 1.9 micrograms/mL of dextromoramide, 0.4 micrograms/mL of methadone, and 0.4 micrograms/mL of lidocaine. A serum alcohol analysis performed using headspace gas chromatography was negative.

Adult↗

PubMed2001

Chiral analysis of methylphenidate and dextromoramide by capillary electrophoresis.

Capillary electrophoretic methods have been developed to separate the enantiomers of methylphenidate (MPH) and dextromoramide. For MPH separation was achieved with heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD) as chiral selector in a 100 mM phosphoric acid buffer adjusted to pH 3.0 with triethanolamine. Commercial samples of D,L-erytho-MPH HCl and D,L-threo-MPH HCl were analysed using the method. There was no evidence of the presence of D,L-threo-MPH HCl in D,L-erytho-MPH HCl and vice versa. The ratio of the enantiomers was determined for each diastereoisomer. Hydroxypropyl-beta-cyclodextrin was the chiral selector of choice for the chiral separation of the enantiomers of moramide. The separation which gave a resolution of about 3.5 was achieved in 4 min using only a 6 cm of length of capillary. In a sample of dextro-R-moramide tartrate only a small quantity (4.9% w/w) of levo-S-moramide was detected with this method.

Buffers↗

PubMed1996

Dextromoramide pharmacokinetics following sublingual administration.

The extent of absorption and other pharmacokinetic parameters of dextromoramide following sublingual administration were assessed in five patients receiving chronic opioid analgesia. The use of the standard 5 mg tablet formulation was associated with negligible absorption in two patients, a prolonged time to peak concentration in the other three and substantial variability in clearance. The study concluded that the standard tablet formulation cannot be recommended for sublingual use where reliable, rapid onset analgesia is required.

Absorption↗

PubMed1989

Toxicological findings after fatal dextromoramide injection.

A death involving dextromoramide injection is presented. The drug was analyzed in whole blood, bile, stomach contents, kidney, brain and liver. The whole blood concentration was 1526 ng/ml. The results are compared with the existing literature.

Adult↗