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Effects of route of administration on neural exposure to platinum-based chemotherapy treatment: a pharmacokinetic study in rat
NeuroToxicology ( IF 3.4 ) Pub Date : 2021-08-04 , DOI: 10.1016/j.neuro.2021.08.002
Stephen N Housley 1 , Travis M Rotterman 2 , Paul Nardelli 2 , Dario I Carrasco 2 , Richard K Noel 3 , Laura O'Farrell 3 , Timothy C Cope 4
Affiliation  

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.



中文翻译:

给药途径对铂类化学疗法神经暴露的影响:大鼠药代动力学研究

对化疗引起的神经毒性 (CIN) 的有效临床治疗的持续需求促使对 CIN 的临床前模型的转化相关性进行批判性评估。本研究旨在首次对体内暴露的神经组织进行定量评估在两种常用给药方案期间和之后使用铂类抗癌化合物奥沙利铂 (OX):临床上使用的缓慢 IV 输注和临床前使用的快速 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态存在差异,但神经毒性的关键驱动因素,例如峰值浓度和暴露,在两种给药途径中没有差异。我们得出结论,OX 给药的 IP 途径在 CIN 啮齿动物模型中实现了神经组织的临床相关药代动力学暴露。

更新日期:2021-08-15
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