Effects of route of administration on neural exposure to platinum-based chemotherapy treatment: a pharmacokinetic study in rat.

Effects of route of administration on neural exposure to platinum-based chemotherapy treatment: a pharmacokinetic study in rat.
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不同给药途径对含铂化疗药物神经暴露的影响:大鼠药代动力学研究。

DOI:
10.1016/j.neuro.2021.08.002
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发表时间:
2021-09
期刊:
影响因子:
3.4
通讯作者:
Cope, Timothy C.
Cope, Timothy C.
中科院分区:
医学3区
文献类型:
--
作者:
Housley, Stephen N.;Rotterman, Travis M.;Nardelli, Paul;Carrasco, Dario I.;Noel, Richard K.;O'Farrell, Laura;Cope, Timothy C.

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对化疗诱导的神经毒性(CIN)的有效临床治疗的持续需求促使对CIN的临床前模型的翻译相关性进行严格评价。本研究旨在提供两种常用给药方案期间和之后体内暴露于铂类抗癌化合物奥沙利铂(OX)的神经组织的首次定量评价:临床使用的缓慢IV输注和临床前使用的推注IP注射。背根神经节的电感耦合等离子体质谱分析表明,虽然铂分布的时间动力学存在差异,但神经毒性的关键驱动因素(例如峰浓度和暴露量)在两种给药途径之间没有差异。我们得出的结论是,在啮齿动物CIN模型中,IP途径给予OX可实现神经组织的临床相关药代动力学暴露。
The persisting need for effective clinical treatment of chemotherapy-induced neurotoxicity (CIN) motivates critical evaluation of preclinical models of CIN for their translational relevance. The present study aimed to provide the first quantitative evaluation of neural tissue exposed in vivo to a platinum-based anticancer compound, oxaliplatin (OX) during and after two commonly used dosing regimens: slow IV infusion used clinically and bolus IP injection used preclinically. Inductively-coupled plasma mass spectrometry analysis of dorsal root ganglia indicated that while differences in the temporal dynamics of platinum distribution exist, key drivers of neurotoxicity, e.g. peak concentrations and exposure, were not different across the two routes of administration. We conclude that the IP route of OX administration achieves clinically relevant pharmacokinetic exposure of neural tissues in a rodent model of CIN.
DOI: 10.33176/aacb-19-00024
发表时间: 2019-08-01
期刊: The Clinical biochemist. Reviews
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