Physiologically-based pharmacokinetic and pharmacodynamic models for gemcitabine and birinapant in pancreatic cancer xenografts.
Physiologically-based pharmacokinetic and pharmacodynamic models for gemcitabine and birinapant in pancreatic cancer xenografts.
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DOI：
10.1007/s10928-018-9603-z
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发表时间：
2018-10
影响因子：
2.5
通讯作者：
Jusko WJ
中科院分区：
文献类型：
--
作者：
Zhu X;Trueman S;Straubinger RM;Jusko WJ
吉西他滨和birinapant组合的抗癌作用在体外PANC-1细胞中被证明是协同的。在这项研究中，来自实验和文献的药代动力学信息被用来开发完整的基于生理学的药代动力学（PBPK）模型，表征个别药物。预测的肿瘤内药物浓度用作异种移植小鼠模型中治疗介导的肿瘤体积变化的关联PBPK/PD模型内的驱动力。药物组合在体内的功效在数学上被评价为表现出加和性。为体外细胞培养中的药物作用开发的网络模型成功地应用于将体内肿瘤药物浓度与肿瘤生长抑制联系起来，结合了更多的机制特征，并解释了体外和体内不同的药物相互作用结果。
The anticancer effects of combined gemcitabine and birinapant were demonstrated as synergistic in PANC-1 cells in vitro. In this study, pharmacokinetic information derived from experiments and the literature was utilized to develop full physiologically-based pharmacokinetic (PBPK) models that characterize individual drugs. The predicted intra-tumor drug concentrations were used as the driving force within a linked PBPK/PD model for treatment-mediated changes in tumor volume in a xenograft mouse model. The efficacy of the drug combination in vivo was evaluated mathematically as exhibiting additivity. The network model developed for drug effects in the in vitro cell cultures was applied successfully to link the in vivo tumor drug concentrations with tumor growth inhibition, incorporating more mechanistic features and accounting for disparate drug interaction outcomes in vitro and in vivo.
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影响因子：
--
作者：
Ebrahem Q;Mahfouz RZ;Ng KP;Saunthararajah Y
通讯作者：
Saunthararajah Y
影响因子：
3
作者：
Hurwitz, Herbert I.;Smith, David C.;Pitot, Henry C.;Brill, Jeffrey M.;Chugh, Rashmi;Rouits, Elisabeth;Rubin, Joseph;Strickler, John;Vuagniaux, Gregoire;Sorensen, J. Mel;Zanna, Claudio
通讯作者：
Zanna, Claudio
影响因子：
13.5
作者：
Bai, Longchuan;Smith, David C.;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
5.7
作者：
Benetatos, Christopher A.;Mitsuuchi, Yasuhiro;Chunduru, Srinivas K.
通讯作者：
Chunduru, Srinivas K.
影响因子：
5.8
作者：
BOUFFARD, DY;LALIBERTE, J;MOMPARLER, RL
通讯作者：
MOMPARLER, RL