代谢和处置vatalanib (PTK787 / zk - 222584)的癌症患者。

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Jost LM, Gschwind惠普,Jalava T,王Y, Guenther C, Souppart C, Rottmann,登纳K, Waldmeier F, G,总值马森E, Laurent D

代谢和处置vatalanib (PTK787 / zk - 222584)的癌症患者。

药物金属底座Dispos。2006年11月,34 (11):1817 - 28。Epub 2006 8月1。

PubMed ID

16882767 (在PubMed

]

文摘

Vatalanib (PTK787 / zk - 222584)是一种新型口服抗血管新生的分子抑制所有已知的血管内皮生长因子受体。Vatalanib正在调查中对实体肿瘤的治疗。性格和生物转化vatalanib研究在一个非盲、单中心研究晚期癌症患者。七个病人都被赋予了一项单一的口头(14)C-radiolabeled剂量1000毫克的vatalanib管理在稳定状态下,连续获得经过14每日口服剂量1000毫克的nonradiolabeled vatalanib。血浆、尿液和粪便分析放射性,vatalanib及其代谢物。代谢产物的高效液相色谱测定模式耦合与离线微型板块固体闪烁计数和放射性检测质。Vatalanib耐受性良好。大多数的不利影响与常见的毒性1或2级标准。两个病人稳定疾病至少7个月。血浆C (max)的值(14)C放射性(38.3 + / - 26.0 microM; mean +/- S.D., n = 7) and vatalanib (15.8 +/- 9.5 microM) were reached after 2 and 1.5 h (median), respectively, indicating rapid onset of absorption. Terminal elimination half-lives in plasma were 23.4 +/- 5.5 h for (14)C radioactivity and 4.6 +/- 1.1 h for vatalanib. Vatalanib cleared mainly through oxidative metabolism. Two pharmacologically inactive metabolites, CGP-84368/ZK-260120 [(4-chlorophenyl)-[4-(1-oxy-pyridin-4-yl-methyl)-phthalazin-1-yl]-amine] and NVP-AAW378/ZK-261557 [rac-4-[(4-chloro-phenyl)amino]-alpha-(1-oxido-4-pyridyl)phthalazine-1-methanol], having systemic exposure comparable to that of vatalanib, contributed mainly to the total systemic exposure. Vatalanib and its metabolites were excreted rapidly and mainly via the biliary-fecal route. Excretion of radioactivity was largely complete, with a radiocarbon recovery between 67% and 96% of dose within 7 days (42-74% in feces, 13-29% in urine).

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药物

Vatalanib