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dc.contributor.authorSkulberg, Arne Kristian
dc.contributor.authorTylleskär, Ida
dc.contributor.authorNilsen, Turid
dc.contributor.authorSkarra, Sissel
dc.contributor.authorSalvesen, Øyvind
dc.contributor.authorSand, Trond
dc.contributor.authorLoftsson, Thorsteinn
dc.contributor.authorDale, Ola
dc.date.accessioned2019-04-10T07:53:15Z
dc.date.available2019-04-10T07:53:15Z
dc.date.created2018-07-01T14:06:36Z
dc.date.issued2018
dc.identifier.citationEuropean Journal of Clinical Pharmacology. 2018, 1-11.nb_NO
dc.identifier.issn0031-6970
dc.identifier.urihttp://hdl.handle.net/11250/2593952
dc.description.abstractPurpose This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg. Methods Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. Results The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02–p < 0.001). Heat pain threshold showed no statistical difference. Conclusions A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose.nb_NO
dc.language.isoengnb_NO
dc.publisherSpringer Berlin Heidelbergnb_NO
dc.titlePharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteersnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionacceptedVersionnb_NO
dc.source.pagenumber1-11nb_NO
dc.source.journalEuropean Journal of Clinical Pharmacologynb_NO
dc.identifier.doi10.1007/s00228-018-2443-3
dc.identifier.cristin1594996
cristin.unitcode194,65,25,0
cristin.unitcode194,65,20,0
cristin.unitcode194,65,30,0
cristin.unitnameInstitutt for sirkulasjon og bildediagnostikk
cristin.unitnameInstitutt for samfunnsmedisin og sykepleie
cristin.unitnameInstitutt for nevromedisin og bevegelsesvitenskap
cristin.ispublishedtrue
cristin.fulltextpreprint
cristin.qualitycode2


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