Population Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Kinase Inhibitor, in Patients With Advanced Solid Tumors.
Population Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Kinase Inhibitor, in Patients With Advanced Solid Tumors.
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DOI：
10.1002/jcph.1974
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发表时间：
2022-03
影响因子：
2.9
通讯作者：
Gupta, Neeraj
中科院分区：
文献类型：
--
作者：
Zhou, Xiaofei;Ouerdani, Aziz;Diderichsen, Paul Matthias;Gupta, Neeraj
使用2项I期和1项II期临床研究中198例接受TAK-931（一种细胞分裂周期7激酶抑制剂）口服给药（30 - 150 mg，每日一次，多次给药方案）的患者的数据，进行了群体药代动力学（PK）分析，以表征晚期实体瘤成人患者中TAK-931 PK的患者间变异性来源。具有2个转运室的2室模型描述了吸收和一级线性消除，充分描述了TAK-931的PK。TAK-931的表观口服清除率（CL/F）估计为38 L/h，终末半衰期估计约为6小时。肌酐清除率（CrCL）被确定为CL/F的协变量，体重被确定为CL/F、表观中心分布容积和表观房室间清除率的协变量。使用最终模型进行的模拟表明，认为CrCL（≥35 mL/min）或体重（29.8 - 127 kg）对TAK-931全身暴露量的影响无临床意义，表明无需调整剂量以考虑体重或肾功能（CrCL ≥35 mL/min）。性别、年龄（36 - 88岁）、人种和轻度肝损害对TAK-931的CL/F无影响。总之，群体PK分析支持全球背景下亚洲和西方癌症患者中TAK-931的起始剂量相同。
A population pharmacokinetic (PK) analysis was conducted to characterize sources of interpatient variability on the PK of TAK‐931, a cell division cycle 7 kinase inhibitor, in adult patients with advanced solid tumors using data from 198 patients who received oral TAK‐931 over the range of 30 to 150 mg once daily in multiple dosing schedules in 2 phase 1 and 1 phase 2 clinical studies. A 2‐compartment model with 2 transit compartments describing the absorption and first‐order linear elimination adequately described the PK of TAK‐931. The apparent oral clearance (CL/F) of TAK‐931 was estimated to be 38 L/h, and the terminal half‐life was estimated to be approximately 6 hours. Creatinine clearance (CrCL) was identified as a covariate on CL/F, and body weight as a covariate on CL/F, apparent central volume of distribution, and apparent intercompartmental clearance. Simulations using the final model indicated that the effect of CrCL (≥35 mL/min) or body weight (29.8‐127 kg) on TAK‐931 systemic exposures was not considered clinically meaningful, suggesting that no dose adjustments were necessary to account for body weight or renal function (CrCL ≥35 mL/min). Sex, age (36‐88 years), race, and mild hepatic impairment had no impact on the CL/F of TAK‐931. Taken together, the population PK analysis supports the same starting dose of TAK‐931 in Asian and Western cancer patients in a global setting.
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DOI：
10.1002/psp4.12161
发表时间：
2017-02
期刊：
CPT: pharmacometrics & systems pharmacology
影响因子：
--
作者：
Nguyen TH;Mouksassi MS;Holford N;Al-Huniti N;Freedman I;Hooker AC;John J;Karlsson MO;Mould DR;Pérez Ruixo JJ;Plan EL;Savic R;van Hasselt JG;Weber B;Zhou C;Comets E;Mentré F;Model Evaluation Group of the International Society of Pharmacometrics (ISoP) Best Practice Committee
通讯作者：
Model Evaluation Group of the International Society of Pharmacometrics (ISoP) Best Practice Committee
DOI：
10.1007/s10928-007-9066-0
发表时间：
2007-10-01
影响因子：
2.5
作者：
Savic, Radojka M.;Jonker, Danieel M.;Karlsson, Mats O.
通讯作者：
Karlsson, Mats O.
影响因子：
3.5
作者：
Mould, D R;Upton, R N
通讯作者：
Upton, R N
影响因子：
9.7
作者：
Cheng, An Ning;Jiang, Shih Sheng;Lee, Alan Yueh-Luen
通讯作者：
Lee, Alan Yueh-Luen
影响因子：
3.4
作者：
Hou, Yun;Wang, Hua-Qing;Ba, Yi
通讯作者：
Ba, Yi