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Disposition of Imatinib and Its Metabolite CGP74588 in a Patient with Chronic Myelogenous Leukemia and Short‐Bowel Syndrome
Author(s) -
Beumer Jan H.,
Natale James J.,
Lagattuta Theodore F.,
Raptis Anastasios,
Egorin Merrill J.
Publication year - 2006
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.26.7.903
Subject(s) - imatinib , chronic myelogenous leukemia , imatinib mesylate , medicine , pharmacokinetics , leukemia , gastroenterology , bioavailability , pharmacology , myeloid leukemia
Imatinib mesylate, licensed to treat chronic myelogenous leukemia and gastrointestinal stromal tumors, is metabolized by means of cytochrome P450 3A and excreted primarily in the bile. Although the bioavailability of imatinib mesylate is more than 97%, the exact gastrointestinal site of its absorption is unknown. Liquid chromatography‐mass spectrometry was used to quantitate imatinib and its metabolite CGP74588 in the plasma and jejunostomy output of a patient with newly diagnosed chronic myelogenous leukemia. She had previously lost most of her small bowel and all of her colon as a result of mesenteric artery thrombosis and radiation‐induced colitis and/or proctitis. Imatinib pharmacokinetics in plasma indicated that approximately 20% of the patient's 400‐mg dose was absorbed. The jejunostomy output contained 338 mg of imatinib, which was consistent with 320 mg of a nonabsorbed dose plus approximately 23% of the absorbed dose being excreted unchanged in the bile. These data indicate the importance of considering gastrointestinal anatomic abnormalities or disease states when oral imatinib is dosed.