Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials.

ABSTRACT:

Aims

The aims of the study were to characterize the pharmacokinetics (PK) of selumetinib (AZD6244; ARRY-142886), a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor in clinical development for various indications, and its N-desmethyl metabolite in healthy volunteers, and evaluate clinically important covariates.

Methods

A pooled-population PK analysis was performed using a nonlinear mixed-effects approach with plasma concentration data from 346 subjects who received single oral doses of selumetinib 20-75 mg across 10 phase I studies. Absolute bioavailability was determined using intravenous [¹⁴ C] selumetinib.

Results

A two-compartment linear model with sequential zero-first order absorption and a lag time for the zero-order process was described

SUBMITTER: Patel P 

PROVIDER: S-EPMC5736843 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature