{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["81(2)"],"submitter":["Kyhl LE"],"pubmed_abstract":["<h4>Aims</h4>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 μ-opioid receptor occupancy by simulations in the target population.<h4>Methods</h4>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 μ-opioid occupancy.<h4>Results</h4>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 l h(-1) and a central volume of distribution of 266 l. Absolute oral bioavailability was estimated to 41% without food intake and with food about 53%. Simulation of the μ-opioid receptor occupancy shows that the 95% confidence bound is within or above 60-90% occupancy for up to 22-24 h after a single dose of 20 mg nalmefene.<h4>Conclusions</h4>A robust population PK model for nalmefene was developed. Based on the concentration-occupancy model the μ-opioid receptor occupancy after a single 20 mg dose of nalmefene is predicted to be above the target therapeutic occupancy for about 24 h in about 95% of the target population."],"journal":["British journal of clinical pharmacology"],"pagination":["290-300"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4833148"],"repository":["biostudies-literature"],"pubmed_title":["Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy."],"pmcid":["PMC4833148"],"pubmed_authors":["Li S","Faerch KU","Soegaard B","Larsen F","Areberg J","Kyhl LE"],"additional_accession":[]},"is_claimable":false,"name":"Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy.","description":"<h4>Aims</h4>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 μ-opioid receptor occupancy by simulations in the target population.<h4>Methods</h4>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 μ-opioid occupancy.<h4>Results</h4>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 l h(-1) and a central volume of distribution of 266 l. Absolute oral bioavailability was estimated to 41% without food intake and with food about 53%. Simulation of the μ-opioid receptor occupancy shows that the 95% confidence bound is within or above 60-90% occupancy for up to 22-24 h after a single dose of 20 mg nalmefene.<h4>Conclusions</h4>A robust population PK model for nalmefene was developed. Based on the concentration-occupancy model the μ-opioid receptor occupancy after a single 20 mg dose of nalmefene is predicted to be above the target therapeutic occupancy for about 24 h in about 95% of the target population.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Feb","modification":"2025-04-25T17:29:21.491Z","creation":"2019-03-27T02:11:38Z"},"accession":"S-EPMC4833148","cross_references":{"pubmed":["26483076"],"doi":["10.1111/bcp.12805"]}}