代谢和处置甲磺酸伊马替尼在健康志愿者。
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Gschwind惠普Pfaar U, Waldmeier F, Zollinger M,说话的C, Zbinden P,海耶斯,Pokorny R, Seiberling M, Ben-Am M,彭B, G
代谢和处置甲磺酸伊马替尼在健康志愿者。
药物金属底座Dispos。2005年10月,33(10):1503 - 12所示。doi: 10.1124 / dmd.105.004283。Epub 2005年7月8日。
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16006570 (在PubMed]
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甲磺酸伊马替尼(格列卫、GLIVEC以前STI571)前所未有的有效性作为一线治疗治疗慢性粒细胞性白血病的所有阶段和转移性和不可切除的恶性胃肠道间质瘤。性格和伊马替尼的生物转化研究在四个男性健康志愿者单剂量口服后239毫克(14)C-labeled甲磺酸伊马替尼。生物体液分析总辐射、伊马替尼及其主要代谢物CGP74588。代谢物与离线模式radio-high-performance液相色谱测定微型板块固体闪烁计数和液相色谱-光谱法的特征。伊马替尼治疗耐受良好,没有严重的不良事件。吸收快速(t (max) 1 - 2小时),完成与伊马替尼的主要放射性化合物等离子体。最大血浆浓度分别为0.921 + / - 0.095杯/毫升(意味着美国南达科他州+ / -伊马替尼,n = 4)和0.115 + / - 0.026杯/毫升的药物活性N-desmethyl代谢物(CGP74588)。意味着等离子体终端消除半衰期分别为13.5 + / - 0.9 h,伊马替尼为CGP74588 20.6 + / - 1.7 h, 57.3 + / - 12.5 h (14) C放射性。伊马替尼是主要通过氧化代谢。 Approximately 65 and 9% of total systemic exposure [AUC(0-24 h) (area under the concentration time curve) of radioactivity] corresponded to imatinib and CGP74588, respectively. The remaining proportion corresponded mainly to oxidized derivatives of imatinib and CGP74588. Imatinib and its metabolites were excreted predominantly via the biliary-fecal route. Excretion of radioactivity was slow with a mean radiocarbon recovery of 80% within 7 days (67% in feces, 13% in urine). Approximately 28 and 13% of the dose in the excreta corresponded to imatinib and CGP74588, respectively.
