Assuntos
Dextromoramida/farmacocinética , Hipnóticos e Sedativos/farmacocinética , Metadona/farmacocinética , Metadona/uso terapêutico , Entorpecentes/farmacocinética , Piridinas/farmacocinética , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adulto , Dextromoramida/efeitos adversos , Aprendizagem por Discriminação , Relação Dose-Resposta a Droga , Euforia/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Taxa de Depuração Metabólica , Entorpecentes/administração & dosagem , Entorpecentes/uso terapêutico , Piridinas/efeitos adversos , Síndrome de Abstinência a Substâncias/sangue , Síndrome de Abstinência a Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Falha de Tratamento , ZolpidemRESUMO
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.
Assuntos
Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Dextromoramida/farmacocinética , Dependência de Heroína/reabilitação , Metadona/uso terapêutico , Adulto , Idoso , Analgésicos Opioides/sangue , Área Sob a Curva , Calibragem , Dextromoramida/sangue , Meia-Vida , Dependência de Heroína/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Reluctance to commence treatment with a Step 3 drug on the Analgesic Stepladder is a common reason for failure to manage chronic severe pain in many situations. The fourth article in the series reviews the potent opioid analgesics for oral use and in doing so addresses the various prejudices that surface when such therapy is denied.
Assuntos
Analgésicos Opioides/uso terapêutico , Dor/tratamento farmacológico , Administração Oral , Analgésicos Opioides/farmacocinética , Doença Crônica , Dextromoramida/farmacocinética , Dextromoramida/uso terapêutico , Esquema de Medicação , Humanos , Hidromorfona/farmacocinética , Hidromorfona/uso terapêutico , Morfina/farmacocinética , Morfina/uso terapêuticoRESUMO
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.
Assuntos
Analgésicos Opioides/farmacocinética , Dextromoramida/farmacocinética , Absorção , Administração Sublingual , Idoso , Analgesia/métodos , Analgésicos Opioides/administração & dosagem , Dextromoramida/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
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.
Assuntos
Dextromoramida/análise , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/química , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Detecção do Abuso de Substâncias , Dextromoramida/farmacocinética , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/metabolismo , Cabelo/metabolismo , Dependência de Heroína/diagnóstico , Dependência de Heroína/metabolismo , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/metabolismo , Abuso de Substâncias por Via Intravenosa/diagnóstico , Abuso de Substâncias por Via Intravenosa/metabolismoRESUMO
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.
Assuntos
Dextromoramida/farmacocinética , Animais , Cromatografia Gasosa , Injeções Intraperitoneais , Masculino , Ratos , Ratos Endogâmicos , Distribuição TecidualRESUMO
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.
Assuntos
Dextromoramida/envenenamento , Adulto , Dextromoramida/farmacocinética , Feminino , Humanos , Masculino , Distribuição TecidualRESUMO
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.
Assuntos
Dextromoramida/farmacocinética , Idoso , Analgésicos Opioides/farmacocinética , Anestesia Geral , Dextromoramida/sangue , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos VascularesRESUMO
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.
Assuntos
Dextromoramida/farmacocinética , Adolescente , Adulto , Dextromoramida/efeitos adversos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Medicação Pré-AnestésicaRESUMO
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.