Clinckers Ralph, Smolders Ilse, Vermoesen Katia, Michotte Yvette, Danhof Meindert, Voskuyl Rob, Della Pasqua Oscar
Vrije Universiteit Brussel (VUB), Pharmaceutical Institute, Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry and Drug Analysis (labo FASC), Laarbeeklaan 103, Building G, 1090 Brussels, Belgium.
Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1267-77. doi: 10.1517/17425250903146903.
Biophase concentrations of antiepileptic drugs can differ significantly from pharmacokinetics in plasma. A crucial determinant in the disposition of antiepileptic drugs to the brain is represented by the blood-brain barrier. There is growing evidence that this barrier can alter the availability of antiepileptic drugs at the target site. The permeability of the blood-brain barrier becomes particularly relevant in epileptic conditions and in drug refractory situations. In vivo, intracerebral microdialysis is a valuable technique to determine biophase drug concentrations as it enables investigation of antiepileptic drug transport and distribution in the brain as a function of time. The present review illustrates that intracerebral microdialysis is an indispensable tool for the assessment of the pharmacokinetics of antiepileptic drugs. In addition, we demonstrate how microdialysis data can be used in conjunction with mechanism-based pharmacokinetic/pharmacodynamic modeling for dose selection and optimization of the therapeutic regimen for novel compounds.
抗癫痫药物的生物相浓度可能与血浆中的药代动力学有显著差异。血脑屏障是抗癫痫药物在脑内分布的一个关键决定因素。越来越多的证据表明，该屏障会改变抗癫痫药物在靶点的可及性。血脑屏障的通透性在癫痫状态和药物难治性情况下尤为重要。在体内，脑内微透析是一种确定生物相药物浓度的有价值技术，因为它能够研究抗癫痫药物在脑内随时间变化的转运和分布。本综述表明，脑内微透析是评估抗癫痫药物药代动力学不可或缺的工具。此外，我们还展示了如何将微透析数据与基于机制的药代动力学/药效学模型结合使用，以进行新型化合物的剂量选择和治疗方案优化。
