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Methadone Concentration (methadone + concentration)
Selected AbstractsMethadone dose and post-mortem blood concentrationDRUG AND ALCOHOL REVIEW, Issue 4 2002Dr. JOHN R. M. CAPLEHORN Abstract The relationship of methadone dose with post-mortem blood concentration was investigated using data collected from 1994 coronial cases in the Australian state of New South Wales. Data on 31 subjects were summarized using linear regression. The weight-adjusted methadone dose, gender, methadone maintenance treatment status and its interaction with adjusted-dose were all significant predictors of post-mortem blood methadone concentration. Data on the death of a young man from the toxic effects of three daily doses of 30mg methadone are used to give an example of a pair of observed (0.74 mg/l) and predicted (0.48 mg/l) post-mortem blood concentrations. The estimated post-mortem blood concentration for male maintenance patients is at least twice the trough plasma levels estimated from previously published studies of living maintenance patients. The estimated post-mortem blood concentration for female maintenance patients is at least three times the estimated trough level of living subjects. We conclude that post-mortem methadone redistribution is probably the principal cause of the observed differences between males and females in post-mortem blood concentrations and the differences between estimated concentrations for living and deceased subjects. [source] Methadone and impairment in apprehended driversADDICTION, Issue 3 2009Jean-Paul Bernard ABSTRACT Aims According to Norwegian guidelines, patients who are in opioid-assisted rehabilitation programmes are permitted to drive a motor vehicle provided that certain requirements are met. The purpose of this study was to investigate apprehended drivers who had methadone in their blood at the time of apprehension and, further, the relationship between blood methadone concentration and impairment as measured by the clinical test of impairment (CTI). Methods The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyses blood samples from all drivers suspected of driving under the influence of drugs nation-wide. Cases with positive results for methadone in blood were collected over the period 2001,2006. Results A total of 635 drivers with methadone found in their blood samples were identified. The majority of drivers were men (>80%), aged between 30 and 40 years. Methadone was the only psychoactive drug detected in blood in only 10 cases. Benzodiazepines were a frequent finding (in approximately 90% of cases). A significant difference in blood methadone concentration was found between cases where only methadone was detected [median 0.46 mg/l (range 0.19,0.65)] and cases where methadone was detected in combination with other psychoactive drugs [median 0.28 mg/l (range 0.06,1.24)]. A CTI had been carried out, in conjunction with blood sampling, in 577 of the cases. A concentration,impairment relationship was not seen for methadone in these cases. Conclusions Cases of driving impairment involving methadone alone were very rare, with combination use most frequent. No correlation between methadone concentration and impairment as judged by the CTI was seen either for these cases or for the material as a whole. [source] PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in ratsADDICTION BIOLOGY, Issue 1 2010Lucie Chevillard ABSTRACT Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (mu1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (TI) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (TE) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO2 (P < 0.01) and TE (P < 0.001) but only partially on TI (P < 0.001). Naltrindole reduced methadone-related effects on TE (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO2 (P < 0.05) Respiratory effects as a function of plasma R -methadone concentrations showed a decrease in PaO2 (EC50: 1.14 µg/ml) at lower concentrations than those necessary for PaCO2 increase (EC50: 3.35 µg/ml). Similarly, increased TI (EC50: 0.501 µg/ml) was obtained at lower concentrations than those for TE (EC50: 4.83 µg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in TE is caused by mu1- and delta-opioid receptors while increase in TI is caused by mu-ORs. [source] Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. L. LINARDI Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source] | ||||||||||