Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy.

ABSTRACT:

Aims

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.

Methods

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.

Results

A two compartment

SUBMITTER: Kyhl LE 

PROVIDER: S-EPMC4833148 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature