Everolimus alters imatinib blood partition in favour of the erythrocyte.
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 gastro-intestinal stromal tumours. Routine therapeutic drug monitoring of blood plasma versus red blood cells over several years by liquid chromatography coupled tandem mass spectrometry has high-lighted 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.
Prenen
Hans
H
Laboratory for Experimental Oncology, Department of General Medical Oncology, University Hospital Gasthuisberg, Catholic University Leuven, Belgium. hans.prenen@uz.kuleuven.be
Guetens
Gunther
G
De Boeck
Gert
G
Highley
Martin
M
van Oosterom
Allan T
AT
de Bruijn
Ernst A
EA
D000970:Antineoplastic Agents / Q000097:blood*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D000068338:Everolimus; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D010879:Piperazines / Q000097:blood*; D010949:Plasma / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000097:blood*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000068338:Everolimus; D020123:Sirolimus