评估吸收、分布、代谢和排泄的[(14)C] -rucaparib,保利(ADP-ribose)聚合酶抑制剂,在晚期实体肿瘤患者。
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廖M,沃特金斯,纳什E,艾萨克森J,埃特尔J,救生员J,风扇R,沈L, Mutlib, Kemeny V, Papai Z, van Tilburg P,小JJ
评估吸收、分布、代谢和排泄的[(14)C] -rucaparib,保利(ADP-ribose)聚合酶抑制剂,在晚期实体肿瘤患者。
新药投资。2020年6月,38 (3):765 - 775。doi: 10.1007 / s10637 - 019 - 00815 - 2。Epub 2019年6月27日。
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31250355 (在PubMed]
- 文摘
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Rucaparib,保利(ADP-ribose)聚合酶抑制剂,许可用于复发性卵巢、输卵管或原发性腹膜癌。我们特征的吸收、分布、代谢和消除rucaparib 6晚期实体肿瘤患者单剂量口服后[(14)C] -rucaparib 600毫克(大约140 muCi)。总辐射(交易)在血液、血浆、尿液和粪便,用液体闪烁计数测量。不变rucaparib在等离子体浓度测定用验证液相色谱串联质谱分析。最大浓度(Cmax)的交易和不变rucaparib等离子情商是880 ng / mL 428 ng / mL,分别约为4 h后剂量;终端半衰期是交易和rucaparib > 25 h。等离子TRA-time概要文件是平行但高于rucaparib,暗示代谢物在等离子体的存在。意味着血液:Cmax等离子体辐射的比率是1.0和0.8曲线下的面积从0到无穷大。意味着postdose恢复交易是89.3%超过12天(71.9%粪便;尿液中17.4%)。 Unchanged rucaparib and M324 (oxidative metabolite) were the major components in plasma, contributing to 64.0% and 18.6% of plasma radioactivity, respectively. Rucaparib and M324 were the major rucaparib-related components (each approximately 7.6% of dose) in urine, whereas rucaparib was the predominant component (63.9% of dose) in feces. The high fecal recovery of unchanged rucaparib could be attributed to hepatic excretion and/or incomplete oral absorption. Overall, these data suggest that rucaparib is eliminated through multiple pathways, including metabolism and renal and biliary excretion.
