Löscher Wolfgang
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
Epilepsia. 2007;48 Suppl 1:8-13. doi: 10.1111/j.1528-1167.2007.00993.x.
Current estimates indicate that up to one-third of all individuals with epilepsy are refractory to antiepileptic drug (AED) therapy. Moreover, most of these people are resistant to multiple drugs with a wide range of mechanistic actions. These observations suggest that the development of multidrug resistance involves nonspecific, global changes in the brain. The multidrug transporter hypothesis of pharmacoresistant epilepsy proposes that regional-specific overexpression of drug efflux transporters in the blood-brain barrier limits the brain penetration of AEDs. Consequently, drug concentrations are too low to induce antiepileptic effects at target brain sites. Cumulative clinical and experimental data support this hypothesis and offer novel therapeutic approaches for the treatment of drug-resistant epilepsy.
目前的估计表明，高达三分之一的癫痫患者对抗癫痫药物（AED）治疗无效。此外，这些患者中的大多数对多种具有广泛作用机制的药物都有耐药性。这些观察结果表明，多药耐药性的产生涉及大脑中非特异性的整体变化。药物抵抗性癫痫的多药转运体假说提出，血脑屏障中药物外排转运体的区域特异性过表达限制了AEDs进入大脑。因此，药物浓度过低，无法在目标脑区诱导抗癫痫作用。累积的临床和实验数据支持这一假说，并为耐药性癫痫的治疗提供了新的治疗方法。
