Determination of naltrexone and its major metabolite, 6-β-naltrexol, in human plasma using liquid chromatography with electrochemical detection

Davidson, Anna F.; Emm, Thomas; Pieniaszek, Henry J.

doi:10.1016/0731-7085(96)01794-3

Cited by 36 publications

(19 citation statements)

References 13 publications

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“…6-b-naltrexol is biologically active and has a longer half-life (12-18 h) than naltrexone (4-9 h) (Davidson et al, 1996;Ferrari et al, 1998;Verebey et al, 1976;Wall et al, 1981). In the current study, there was marked variability across subjects for serum levels of naltrexone, and there was a fourfold difference in peak serum levels of naltrexone vs 6-bnaltrexol levels.…”

Section: Discussionmentioning

confidence: 99%

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

139

147

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Blockade of brain m-opioid receptor (m-OR) and d-opioid receptor (d-OR) was investigated in recently abstinent alcohol-dependent subjects (N ¼ 21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-b-naltrexol. Regional brain m-OR binding potential (BP) and d-OR K i was measured using [ 11 C]carfentanil (CAR) positron emission tomography (PET) and [11 C]methyl naltrindole ([ 11 C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [ 11 C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean + SD% inhibition ¼ 94.9 + 4.9%). Naltrexone only partially inhibited the [ 11 C]MeNTI K i and there was more variability across subjects (mean + SD% inhibition ¼ 21.1 + 14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of d-OR K i in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of m-OR BP. Peak levels of 6-b-naltrexol were not significantly correlated with % inhibition of m-OR BP or d-OR K i . Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the m-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of d-OR and greater variability in d-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in d-OR blockade by naltrexone and clinical outcomes should be explored.

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Section: Discussionmentioning

confidence: 99%

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

139

147

View full text Add to dashboard Cite

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“…Samples were analysed for naltrexone and the metabolite 6-b -naltrexol [3] by high-performance liquid chromatography (HPLC) using modifications of previously published methods, including a reduced plasma volume (1 ml), a different organic solvent for extraction (dichloromethane : propanol, 95 : 5) [12] and a HPLC mobile phase of 28% acetonitrile in 80 m M phosphate buffer with 2 m M sodium dodecyl sulphate [13] . The coefficients of variation for naltrexone and 6-b -naltrexol were 8 and 10% (1.7 ng ml -1 ) and 3 and 2% (13.6 ng ml -1 ), respectively.…”

Section: Methodsmentioning

confidence: 99%

Plasma concentrations during naltrexone implant treatment of opiate‐dependent patients

Olsen

Christophersen

Frogopsahl

et al. 2004

Brit J Clinical Pharma

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AimsTo evaluate individual variations in plasma concentrations over time in patients with naltrexone implants. MethodsTen opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite b -naltrexol. ResultsThe median naltrexone C max was 12.3 (range 5.8-22.1) ng ml -1 , the median T max was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml -1 was 55 (range 30-80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation. ConclusionMarked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.

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“…Its mechanism of action in alcohol dependence is not fully understood, but, as an opioid-receptor antagonist, it is likely to be due to the modulation of the dopaminergic mesolimbic pathway, which ethanol is believed to activate [5]. Many techniques have been developed for determination of NTX in pharmaceutical and clinical preparations such as high performance liquid chromatography (HPLC) [6][7][8], gas-liquid chromatography [9][10][11], gas chromatography-mass spectrometry (GC-MS) [12,13], LC-MS/MS [14], chemiluminescence [15], thin layer chromatography (TLC) [16], LC with electrochemical detection [17,18], attenuated total reflectance FT-IR spectrometry [5], LC-MS [19], spectrofluorimetry [4], LC-electrospray ionization (ESI) tandem mass spectrometry [20] and GC-negative ion chemical ionization-MS [21]. Spectrophotometric and chromatographic methods usually suffer from some disadvantages such as, expensive instrumentation, lengthy and tedious sample preparation, long analysis times and low sensitivity and selectivity.…”

Section: Introductionmentioning

confidence: 99%

Application of Glassy Carbon Electrode Modified with a Bilayer of Multiwalled Carbon Nanotube and Polypyrrole Doped with Nitrazine Yellow for Voltammetric Determination of Naltrexone

2011

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A new sensitive electrochemical sensor was fabricated based on a layer by layer process. In this process the glassy carbon electrode (GCE) is first coated by a thin film of multiwalled carbon nanotubes (MWCNTs). In the next step, the electropolymerization of pyrrole in the presence of Nitrazine Yellow (NY) as a dopant anion is performed on the surface of the MWCNTs precoated electrode. The electrochemical response characteristics of the modified electrode toward naltrexone (NTX) were studied by means of linear sweep voltammetry (LSV). A remarkable increase (~19 times) was observed in the anodic peak current of NTX on the surface of the modified electrode relative to the bare GCE. The effects of experimental parameters on the electrode response such as, drop size of the cast MWCNTs suspension, pH of the supporting electrolyte, accumulation conditions and the number of cycles in the electropolymerization process were investigated. Under the optimum conditions, the modified electrode showed a wide linear response to the concentration of NTX in the range of 4.0 10À5 mol L À1 with a detection limit of 12 nmol L À1. The prepared sensor exhibited high sensitivity, stability and good reproducibility for the determination of NTX. This sensor was successfully applied for the accurate determination of trace amounts of NTX in pharmaceutical and clinical preparations.

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Determination of naltrexone and its major metabolite, 6-β-naltrexol, in human plasma using liquid chromatography with electrochemical detection

Cited by 36 publications

References 13 publications

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Plasma concentrations during naltrexone implant treatment of opiate‐dependent patients

Application of Glassy Carbon Electrode Modified with a Bilayer of Multiwalled Carbon Nanotube and Polypyrrole Doped with Nitrazine Yellow for Voltammetric Determination of Naltrexone

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