Beumer Jan H, Natale James J, Lagattuta Theodore F, Raptis Anastasios, Egorin Merrill J
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-1863, USA.
Pharmacotherapy. 2006 Jul;26(7):903-7. doi: 10.1592/phco.26.7.903.
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.
甲磺酸伊马替尼被批准用于治疗慢性粒细胞白血病和胃肠道间质瘤，它通过细胞色素P450 3A进行代谢，主要经胆汁排泄。尽管甲磺酸伊马替尼的生物利用度超过97%，但其确切的胃肠道吸收部位尚不清楚。采用液相色谱-质谱联用技术对一名新诊断的慢性粒细胞白血病患者的血浆和空肠造口排泄物中的伊马替尼及其代谢产物CGP74588进行定量分析。由于肠系膜动脉血栓形成以及放射性结肠炎和/或直肠炎，该患者此前已切除大部分小肠和全部结肠。血浆中的伊马替尼药代动力学表明，该患者400毫克剂量的药物约20%被吸收。空肠造口排泄物中含有338毫克伊马替尼，这与320毫克未吸收剂量加上约23%的吸收剂量以原形经胆汁排泄的情况相符。这些数据表明，在口服甲磺酸伊马替尼给药时，考虑胃肠道解剖异常或疾病状态的重要性。
