Everolimus alters imatinib blood partition in favour of the erythrocyte

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Abstract

The signal transduction inhibitor imatinib is one of the latest breakthroughs in cancer pharmacotherapy. It is administered orally over prolonged periods of time for the treatment of gastrointestinal stromal tumours. Routine therapeutic drug monitoring of blood plasma versus red blood cells over several years by liquid chromatography coupled tandem mass spectrometry has highlighted a very intriguing phenomenon. Imatinib plasma availability decreases dramatically owing to a significant shift in the partition ratio of red blood cells versus plasma. The shift is enforced by combination with everolimus, another signal transduction inhibitor. These data warrant routine erythrocyte versus plasma monitoring to prevent unexpected alterations in drug efficacy during long-term treatment.

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