TY - JOUR
T1 - Pharmacokinetics of single doses of methadone and buprenorphine in blood and oral fluid in healthy volunteers and correlation with effects on psychomotor and cognitive functions
AU - Strand, Maren Cecilie
AU - Ramaekers, Johannes G
AU - Gjerde, Hallvard
AU - Mørland, Jørg
AU - Vindenes, Vigdis
N1 - Funding Information:
From the *Department of Forensic Sciences, Oslo University Hospital; and †Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ‡Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, University of Maastricht, Maastricht, the Netherlands; and §Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway. Received February 6, 2019; accepted after revision May 14, 2019. Reprints: Maren Cecilie Strand, MD, Department of Forensic Sciences, Oslo University Hospital, PO Box 4950 Nydalen, 0424 Oslo, Norway (e‐mail: macest@ous-hf.no). This study was funded by the Norwegian Ministry of Transport and Communications, the Norwegian Institute of Public Health, and Department of Forensic Sciences, Oslo University Hospital. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0271-0749 DOI: 10.1097/JCP.0000000000001077
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019
Y1 - 2019
N2 - PURPOSE: We aimed to study the pharmacokinetics of methadone and buprenorphine in blood and oral fluid after single-dose administration and investigate correlations between concentrations in blood and neurocognitive functions.METHODS: A 5-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study was performed to study the pharmacokinetics and neurocognitive effects of methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) in 22 healthy volunteers. Blood and oral fluid were collected throughout the test days, and drug concentrations in both matrices were analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. On-road driving testing, neurocognitive computerized tests, and subjective questionnaires were performed.RESULTS: Large individual variations in concentrations of methadone and buprenorphine in blood and oral fluid, and accordingly oral fluid/blood drug concentration ratios, were observed. The mean ratio 6.5 hours after drug administration was 2.0 (range, 0.49-7.39) for methadone after both doses. Buprenorphine was not detected above the limit of quantification in blood after 6.5 hours. No significant correlation between methadone concentration in blood and effect was found. Significant correlations were found between buprenorphine concentration in blood and standard deviation of lateral position in the driving test and some measures of reaction time, divided attention, balance, alertness, contentedness. and sleepiness.CONCLUSIONS: Concentrations of methadone and buprenorphine in blood and oral fluid showed large interindividual variations. No concentration-effect correlations were found for methadone, whereas low to moderate correlations were observed between buprenorphine concentration and driving, psychomotor function, and subjective rating of sleep and alertness.
AB - PURPOSE: We aimed to study the pharmacokinetics of methadone and buprenorphine in blood and oral fluid after single-dose administration and investigate correlations between concentrations in blood and neurocognitive functions.METHODS: A 5-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study was performed to study the pharmacokinetics and neurocognitive effects of methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) in 22 healthy volunteers. Blood and oral fluid were collected throughout the test days, and drug concentrations in both matrices were analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. On-road driving testing, neurocognitive computerized tests, and subjective questionnaires were performed.RESULTS: Large individual variations in concentrations of methadone and buprenorphine in blood and oral fluid, and accordingly oral fluid/blood drug concentration ratios, were observed. The mean ratio 6.5 hours after drug administration was 2.0 (range, 0.49-7.39) for methadone after both doses. Buprenorphine was not detected above the limit of quantification in blood after 6.5 hours. No significant correlation between methadone concentration in blood and effect was found. Significant correlations were found between buprenorphine concentration in blood and standard deviation of lateral position in the driving test and some measures of reaction time, divided attention, balance, alertness, contentedness. and sleepiness.CONCLUSIONS: Concentrations of methadone and buprenorphine in blood and oral fluid showed large interindividual variations. No concentration-effect correlations were found for methadone, whereas low to moderate correlations were observed between buprenorphine concentration and driving, psychomotor function, and subjective rating of sleep and alertness.
KW - DRUG CONCENTRATIONS
KW - FOCUS
KW - INTRAVENOUS BUPRENORPHINE
KW - OCULOMOTOR DEFICIT
KW - SUPPORTED LIQUID EXTRACTION
KW - WHOLE-BLOOD
KW - ZOPICLONE
KW - blood
KW - buprenorphine
KW - methadone
KW - neurocognitive
KW - oral fluid
U2 - 10.1097/JCP.0000000000001077
DO - 10.1097/JCP.0000000000001077
M3 - Article
C2 - 31305338
SN - 0271-0749
VL - 39
SP - 489
EP - 493
JO - Journal of Clinical Psychopharmacology
JF - Journal of Clinical Psychopharmacology
IS - 5
ER -