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Zopiclone impairment: Characterization and measurement in an experimental study

Hjelmeland, Knut
Doctoral thesis
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PhD-Hjelmeland-2020.pdf (2.449Mb)
Year
2020
Permanent link
http://urn.nb.no/URN:NBN:no-82578

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  • Institutt for klinisk medisin [5298]
Abstract
Zopiclone is a frequently prescribed hypnotic drug. Related to the therapeutic effects is impairment of cognitive functioning and psychomotor skills. The thesis is based on a double blind, placebo-controlled, crossover, randomized trial in 16 male subjects. The subjects received 5 mg zopiclone, 10 mg zopiclone, 50 g ethanol or placebo on different study days. On each study day pairs of Oral Fluid (OF)/blood were retrieved and several simplified clinical and computerized tests were performed. We found dose/concentration-related impairment of both zopiclone and ethanol for the clinical and the computerized tests. The computerized tests revealed more impairment than the clinical tests. Tests that measure reaction time were more likely to be influenced by zopiclone, tests that measure impulsive responses were more likely to be affected by ethanol. Acute tolerance to tests that measure automative behavior and or reaction time was found for zopiclone. The zopiclone concentration in OF and the OF/blood concentration ratio was dependent on several variables, such as OF sampler device applied, amount of OF delivered and intake of food. We detected zopiclone in OF up to 14 days after intake.
List of papers
Paper I. Hjelmeland K, Gustavsen I, Bernard JP, Mørland J. Can a simple clinical test detect impairment of zopiclone and alcohol? – A randomized controlled trial (2015). For Sci Int 248: 129–133. DOI: 10.1016/j.forsciint.2014.12.028. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.forsciint.2014.12.028
Paper II. Gustavsen I, Hjelmeland K, Bernard JP, Mørland J. Psychomotor performance after intake of zopiclone compared with intake of ethanol: A randomized, controlled, double-blinded trial (2011). J Clin Psychopharmacol 31(4): 481–488. DOI: 10.1097/JCP.0b013e3182214be6. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1097/JCP.0b013e3182214be6
Paper III. Gjerde H, Øiestad EL, Øiestad ÅM, Langødegård M, Gustavsen I, Hjelmeland K, Bernard JP, Christophersen AS. Comparison of zopiclone concentrations in oral fluid sampled with Intercept® Oral Specimen collection device and Statsure Saliva Sampler™ and concentrations in blood (2010). J of Anal Tox 34:590–593. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1093/jat/34.9.590
Paper IV. Hjelmeland K, Gustavsen I, Øiestad EL, Øiestad ÅML, Høiseth G, Mørland J. Zopiclone concentration in oral fluid and blood, after administration of therapeutic doses of zopiclone (2017). For Sci Int 278:177–183. DOI: 10.1016/j.forsciint.2017.07.004. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.forsciint.2017.07.004
 
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