Population pharmacokinetic/pharmacodynamic modelling of the effects of axomadol and its O-demethyl metabolite on pupil diameter and nociception in healthy subjects.

ABSTRACT:

Aim

The aim of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of the active components of axomadol and to quantify their contribution to observed the pupillometric and analgesic (measured through the cold pressor test) effects linking the PD engagement biomarker with clinical response.

Methods

Healthy subjects (n = 74) received either placebo or axomadol orally at doses ranging from 66 mg to 225 mg following multiple dosing regimens in two separate clinical trials. Plasma concentrations of the two enantiomers of axomadol and their metabolites, and PD responses were measured at specific times. The population analysis was performed using NONMEM 7.2.

Results

The kinetics of the parent drug and its metabolite could be describe

SUBMITTER: Mangas-Sanjuan V 

PROVIDER: S-EPMC4917809 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature