{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:53:52Z","timestamp":1787849632782,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,27]],"date-time":"2016-01-27T00:00:00Z","timestamp":1453852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of this study were to develop a population pharmacokinetic (PK) model to describe the PK of nalmefene in healthy subjects and to relate the exposure of nalmefene to the \u03bc\u2010opioid receptor occupancy by simulations in the target population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from nine phase I studies (243 subjects) with extensive blood sampling were pooled and used for the population PK model building. Data from four other phase I studies (85 subjects) were pooled and used as an external validation dataset. Eight subjects from an imaging study contributed occupancy data and the pharmacokinetic\/pharmacodynamic (PK\/PD) relationship was modelled. Combining the population PK model and the PK\/PD relationship enabled simulations to predict \u03bc\u2010opioid occupancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two compartment model with first order absorption best described the nalmefene PK data. The typical subject in the population was estimated to have a systemic clearance of 60.4\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup> and a central volume of distribution of 266\u00a0l. Absolute oral bioavailability was estimated to 41% without food intake and with food about 53%. Simulation of the \u03bc\u2010opioid receptor occupancy shows that the 95% confidence bound is within or above 60\u201390% occupancy for up to 22\u201324\u00a0h after a single dose of 20\u00a0mg nalmefene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A robust population PK model for nalmefene was developed. Based on the concentration\u2013occupancy model the \u03bc\u2010opioid receptor occupancy after a single 20\u00a0mg dose of nalmefene is predicted to be above the target therapeutic occupancy for about 24\u00a0h in about 95% of the target population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12805","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T04:30:27Z","timestamp":1445315427000},"page":"290-300","source":"Crossref","is-referenced-by-count":20,"title":["Population pharmacokinetics of nalmefene in healthy subjects and its relation to \u03bc\u2010opioid receptor occupancy"],"prefix":"10.1111","volume":"81","author":[{"given":"Lars\u2010Erik Broksoe","family":"Kyhl","sequence":"first","affiliation":[{"name":"Clinical &amp; Quantitative Pharmacology H. 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