Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.

ABSTRACT:

Aims

The aim of this phase 1, single centre, open label study in four patients with solid tumours was to determine the absolute bioavailability of a 2 mg oral dose of trametinib. Trametinib is an orally bioavailable, reversible and selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity.

Methods

A microtracer study approach, in which a 5 μg radiolabelled i.v. microdose of trametinib was given concomitantly with an unlabelled 2 mg oral tablet formulation, was used to recover i.v. and oral pharmacokinetic parameters, simultaneously.

Results

The least-squares mean (90% confidence interval) absolute bioavailability of trametinib (2 mg tablet) was 72.3% (50.0%, 104.6%). Median tmax after oral administration was 1.5 h and the geometric mean terminal h

SUBMITTER: Leonowens C 

PROVIDER: S-EPMC4243903 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature