Show simple item record

dc.contributor.authorTylleskär, Ida
dc.contributor.authorSkulberg, Arne Kristian
dc.contributor.authorSkarra, Sissel
dc.contributor.authorNilsen, Turid
dc.contributor.authorDale, Ola
dc.date.accessioned2018-08-28T07:33:31Z
dc.date.available2018-08-28T07:33:31Z
dc.date.created2018-08-24T19:43:57Z
dc.date.issued2018
dc.identifier.issn0031-6970
dc.identifier.urihttp://hdl.handle.net/11250/2559507
dc.description.abstractPurpose Pharmacodynamic studies of naloxone require opioid agonism. Steady state condition may be achieved by remifentanil TCI (target controlled infusion). Opioid agonism can be measured by pupillometry. It is not known whether there are arteriovenous concentration differences for naloxone. The aim was thus to further develop a model for studying pharmacokinetic/pharmacodynamic aspects of naloxone and to explore whether a significant arteriovenous concentration difference for naloxone in humans was present. Methods Relevant authorities approved this study. Healthy volunteers (n = 12) were given 1.0 mg intravenous (IV) naloxone after steady state opioid agonism was obtained by TCI of remifentanil (1.3 ng/ml). Opioid effect was measured by pupillometry. Arterial and venous samples were collected simultaneously before and for 2 h after naloxone administration for quantification of naloxone and remifentanil. Results Arterial remifentanil was in steady state at 12 min. One milligram IV naloxone reversed the effect of remifentanil to 93% of pre-opioid pupil-size within 4 min. The estimated duration of antagonism was 118 min. At that time, the concentration of naloxone was 0.51 ng/ml. The time course of arterial and venous serum concentrations for naloxone was similar, although arterial AUC (area under the curve) was slightly lower (94%) than the venous AUC (p = 0.03). There were no serious adverse events. Conclusion Onset of reversal by IV naloxone was rapid and lasted 118 min. The minimum effective concentration was 0.5 ng/ml. Using TCI remifentanil to obtain a steady-state opioid agonism may be a useful tool to compare new naloxone products.nb_NO
dc.language.isoengnb_NO
dc.publisherSpringer Verlagnb_NO
dc.titlePharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanilnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionacceptedVersionnb_NO
dc.source.journalEuropean Journal of Clinical Pharmacologynb_NO
dc.identifier.doihttps://doi.org/10.1007/s00228-018-2545-y
dc.identifier.cristin1604452
dc.description.localcodeThis is a post-peer-review, pre-copyedit version of an article published in [European Journal of Clinical Pharmacology] Locked until 24.8.2019 due to copyright restrictions. The final authenticated version is available online at: https://doi.org/10.1007/s00228-018-2545-ynb_NO
cristin.unitcode194,65,25,0
cristin.unitnameInstitutt for sirkulasjon og bildediagnostikk
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record