| Autor: |
Cathrine, Leonowens, Carolyn, Pendry, John, Bauman, Graeme C, Young, May, Ho, Frank, Henriquez, Lei, Fang, Royce A, Morrison, Keith, Orford, Daniele, Ouellet |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
British journal of clinical pharmacology. 78(3) |
| ISSN: |
1365-2125 |
| Popis: |
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.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.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 half-life was 11 days. The geometric mean clearance and volume of distribution after i.v. administration were 3.21 l h(-1) and 976 l, respectively, resulting in a terminal elimination half-life of 11 days.Trametinib absolute bioavailability was moderate to high, whereas first pass metabolism was low. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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