ABSTRACT
AIMS: Oral naltrexone is used in the management of both heroin and alcohol dependence. However, poor compliance has limited its clinical utility. The study's objective was to determine the period of therapeutic coverage (>or=2 ng/ml) provided by a 3.3 g naltrexone subcutaneous implant compared with existing data on 1.1 g and 2.2 g implants. METHODS: We assessed free blood naltrexone levels following treatment with a 3.3 g naltrexone implant in heroin dependent patients (n=50) in Perth, Western Australia. Results were compared with previously collated data for patients treated with either a 1.1 g (n=10) or 2.2 g (n=24) implant. RESULTS: Following 3.3 g naltrexone implant treatment, free blood naltrexone levels remained above 2 ng/ml for 145 days (95% CI 125-167). In comparison, 1.1 g or 2.2 g implant treatment resulted in 95 days (95% CI 69-121) and 136 days (95% CI 114-158) coverage, respectively. CONCLUSIONS: The 3.3 g implant provides longer therapeutic coverage than the 1.1 g implant but not significantly longer than the 2.2 g implant.
Subject(s)
Alcoholism/blood , Heroin Dependence/blood , Naltrexone/blood , Narcotic Antagonists/blood , Adult , Alcoholism/drug therapy , Confidence Intervals , Dose-Response Relationship, Drug , Drug Implants , Female , Follow-Up Studies , Heroin Dependence/drug therapy , Humans , Male , Naltrexone/administration & dosage , Narcotic Antagonists/administration & dosage , Retrospective Studies , Time FactorsABSTRACT
The aim of this study was to assess blood free naltrexone and 6-beta-naltrexol levels with time following treatment with sequential sustained-release naltrexone preparations. Data were collected from blood samples analysed independently for naltrexone and 6-beta-naltrexol and from clinical record review at a community heroin treatment clinic in Perth, Western Australia. Five patients received sequential 3.4 g (3.49+/-0.01 g and 3.36+/-0.05 g, respectively) naltrexone implants. The second implant was received on average within 131.2+/-15.67 days of the first implant. The mean length of follow-up was 307.2+/-18.28 days of the first implant. Blood naltrexone levels have the potential to remain above 2 and 1 ng/ml for a total of 390 and 524 days, respectively, and blood 6-beta-naltrexol was maintained above 10 ng/ml for a total of 222 days following insertion of these implants. No patient relapsed to dependent heroin use during the implant coverage period while blood naltrexone concentrations were above 2 ng/ml. Results indicate that blood naltrexone and 6-beta-naltrexol levels can be maintained above therapeutic levels for prolonged periods following use of sequential 3.4 g naltrexone implants. These extended periods of coverage will offer significant benefits for managing the heroin-dependent patient.
Subject(s)
Heroin Dependence/drug therapy , Naltrexone/administration & dosage , Naltrexone/blood , Narcotic Antagonists/administration & dosage , Narcotic Antagonists/blood , Adult , Body Mass Index , Cohort Studies , Delayed-Action Preparations , Drug Administration Schedule , Drug Implants , Female , Follow-Up Studies , Humans , Male , Middle Aged , Naltrexone/analogs & derivatives , Naltrexone/therapeutic use , Narcotic Antagonists/therapeutic use , Retrospective Studies , Time FactorsABSTRACT
This paper describes the application of Headspace/Solid-Phase Microextraction/Gas Chromatography-Mass Spectrometry (HS/SPME/GC-MS) to the recovery and identification of volatile organic compounds in blood and viscera samples from deceased persons. The technique is used as a screening procedure to rapidly obtain information relating to toxicological investigations. The technique is suitable for the detection of volatiles (of wide boiling range) including butane, halothane, toluene, xylenes, and petrol residues in blood and viscera (lung, brain, and body fat).
Subject(s)
Blood Chemical Analysis , Forensic Medicine/methods , Gas Chromatography-Mass Spectrometry/methods , Organic Chemicals/analysis , Adipose Tissue/chemistry , Autopsy , Brain Chemistry , Cadaver , Humans , Lung/chemistry , Postmortem Changes , VolatilizationABSTRACT
This paper details a sensitive and quantitative method for the determination of salbutamol and the detection of terbutaline, clenbuterol, fenoterol, and isoprenaline in postmortem human whole blood and urine. It describes solid-phase extraction using a XtrackT XRDAH515 column, formation of trimethylsilyl derivatives, and analysis by gas chromatography-mass spectrometry-selective ion monitoring.
Subject(s)
Adrenergic beta-Agonists/metabolism , Albuterol/blood , Albuterol/urine , Gas Chromatography-Mass Spectrometry/methods , Adrenergic beta-Agonists/blood , Adrenergic beta-Agonists/urine , Autopsy , Humans , In Vitro Techniques , Ion-Selective Electrodes , Sensitivity and SpecificityABSTRACT
This paper details various rapid and sensitive methods for the extraction and derivatisation of propranolol, metoprolol, sotalol, atenolol, pindolol, timolol, oxprenolol, alprenolol and penbutolol in equine urine and in human post mortem whole blood and urine. Three solid-phase extraction methods are described involving the use of either XtrackT XRDAH515, Bond Elut Certify or Sep-Pak C18 cartridges. Two derivatisation methods are also described involving the formation of cyclised silyl or pentafluoropropionate derivatives with either chloromethyldimethylchlorosilane or pentafluoropropionic anhydride, respectively. Gas chromatographic-mass spectrometry analysis was carried out in select-ion monitoring mode. All these methods were evaluated using drug-free human post mortem blood, urine and equine urine fortified at various levels with the beta-blockers mentioned above. The application of some of these methods on a forensic case study is also presented. This work does not include samples from equine administration trials of beta-blockers.
