Intractable epilepsy and the P-glycoprotein hypothesis

References

• Wirrell EC. Predicting pharmacoresistance in pediatric epilepsy. Epilepsia 2013;54(Suppl 2):19–22.
   PubMed Web of Science ®Google Scholar
• Schmidt D, Sillanpää M. Evidence-based review on the natural history of the epilepsies. Curr Opin Neurol 2012;25:159–63.
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. New Engl J Med 2000;342:314–9.
   PubMed Web of Science ®Google Scholar
• Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51:1069–77.
   PubMed Web of Science ®Google Scholar
• Hao XT, Wong IS, Kwan P. Interrater reliability of the international consensus definition of drug-resistant epilepsy: a pilot study. Epilepsy Behav 2011;22:388–90.
   PubMed Web of Science ®Google Scholar
• Chayasirisobhon S. The mechanisms of medically refractory temporal lobe epilepsy. Acta Neurol Taiwan 2009;18:155–60.
   PubMedGoogle Scholar
• Guo Y, Jiang L. Drug transporters are altered in brain, liver and kidney of rats with chronic epilepsy induced by lithium-pilocarpine. Neurol Res 2010;32:106–12.
   PubMed Web of Science ®Google Scholar
• Scian M, Acchione M, Li M, Atkins WM. Reaction dynamics of ATP hydrolysis catalyzed by P glycoprotein. Biochemistry 2014;53:991–1000.
   PubMed Web of Science ®Google Scholar
• Chin JE, Soffir R, Noonan KE, et al. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol Cell Biol 1989;9(9):3808–20.
   PubMed Web of Science ®Google Scholar
• Aller SG, Yu J, Ward A, et al. Structure of P-Glycoprotein reveals a molecular basis for poly-specific drug binding. Science 2009;323:1718–22.
   PubMed Web of Science ®Google Scholar
• Sugawara I, Akiyama S, Scheper RJ, Itoyama S. Lung resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP. Cancer Lett 1997;112(1):23–31.
   PubMed Web of Science ®Google Scholar
• Croop JM, Raymond M, Haber D, et al. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. Mol Cell Biol 1989;9:1346–50.
   PubMed Web of Science ®Google Scholar
• He SM, Li R, Kanwar JR, Zhou SF. Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1). Curr Med Chem 2011;18:439–81.
   PubMed Web of Science ®Google Scholar
• Chaves C, Shawahna R, Jacob A, et al. Human ABC transporters at blood-CNS interfaces as determinants of CNS drug penetration. Curr Pharm Des 2014;20(10):1450–62.
   PubMed Web of Science ®Google Scholar
• Saglam A, Hayran M, Uner AH. Immunohistochemical expression of multidrug resistance proteins in mature T/NK-cell lymphomas. APMIS 2008;116(9):791–800.
   PubMed Web of Science ®Google Scholar
• Giraud C, Declves X, Perrot JY, et al. High levels of P-glycoprotein activity in human lymphocytes in the first 6 months of life. Clin Pharmacol Ther 2009;85(3):289–95.
   PubMed Web of Science ®Google Scholar
• McCaffrey G, Staatz WD, Sanchez-Covarrubias L, et al. P-glycoprotein trafficking at the blood-brain barrier altered by peripheral inflammatory hyperalgesia. J Neurochem 2012;122(5):962–75.
   PubMed Web of Science ®Google Scholar
• Volk HA, Burkhardt K, Potschka H, et al. Neuronal expression of the drug efflux transporter P-glycoprotein in the rat hippocampus after libic seizures. Neuroscience 2004;123:751–9.
   PubMed Web of Science ®Google Scholar
• Tallis S, Caltana LR, Souto PA, et al. Changes in CNS cells in hyperammonemic portal hypertensive rats. J Neurochem 2014;128:431–44.
   PubMed Web of Science ®Google Scholar
• Volk HA, Loscher W. Multidrug resistance in epilepsy: rats with drug-resistant seizures exhibit enhanced brain expression of P-glycoprotein compared with rats with drug-responsive seizures. Brain 2005;128:1358--68.
   PubMed Web of Science ®Google Scholar
• Bankstahl JP, Löscher W. Resistance to antiepileptic drugs and expression of P-glycoprotein in two rat models of status epilepticus. Epilepsy Res 2008;82(1):70--85.
   PubMed Web of Science ®Google Scholar
• Luurtsema G, Molthoff CF, Windhorst AD, et al. (R)-(S)-[11C] verapamil as PET-tracers for measuring P-glycoprotein function: in vitro and in vivo evaluation. Nucl Med Boil 2002;30:747–51.
   Web of Science ®Google Scholar
• Yang HW, Liu HY, Liu X, et al. Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro. Neurosci Lett 2008;434:299–303.
   PubMed Web of Science ®Google Scholar
• Jing X, Liu X, Wen T, et al. Combined effects of epileptic seizure and phenobarbital induced overexpression of P-glycoprotein in brain of chemically kindled rats. Br J Pharmacol 2010;159:1511–22.
   PubMed Web of Science ®Google Scholar
• Moerman L, Wyffels L, Slaets D, et al. Antiepileptic drugs modulate P-glycoproteins in the brain: a mice study with C-11-desmethylloperamide. Epilepsy Res 2011;94:18–25.
   PubMed Web of Science ®Google Scholar
• Brandt C, Bethmann K, Gastens AM, Löscher W. The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol Dis 2006;24:202–11.
   PubMed Web of Science ®Google Scholar
• Cox DS, Scott KR, Gao H, et al. Influence of multidrug resistance proteins at the blood-brain barrier on the transport and brain distribution of enaminone anticonvulsants. J Pharm Sci 2001;90:1540–52.
   PubMed Web of Science ®Google Scholar
• Cox DS, Scott KR, Gao H, Eddington ND. Effect of P-glycoprotein on the pharmacokinetics and tissue distribution of enaminone anticonvulsants: analysis by population and physiological approaches. J Pharmacol Exp Ther 2002;302:1096–104.
   PubMed Web of Science ®Google Scholar
• Miller DS, Bauer B, Hartz AMS. Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy. Pharmacol Rev 2008;60:196–209.
   PubMed Web of Science ®Google Scholar
• Chen CP, Liu XR, Smith BJ. Utility of Mdr1-gene deficient mice in assessing the impact of P-glycoprotein on pharmacokinetics and pharmacodynamics in drug discovery and development. Curr Drug Metab 2003;4:272–91.
   PubMed Web of Science ®Google Scholar
• Tishler DM, Weinberg KI, Hinton DR, et al. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 1995;36:1–6.
   PubMed Web of Science ®Google Scholar
• Dickens D, Yusof SR, Abbott NJ, et al. A multi-system approach assessing the interaction of anticonvulsants with P-gp. PLoS One 2013;8(5):e64854.
   PubMed Web of Science ®Google Scholar
• Crowe A, Teoh YK. Limited P-glycoprotein mediated efflux for anti-epileptic drugs. J Drug Target 2006;14(5):291–300.
   PubMed Web of Science ®Google Scholar
• Zhang C, Zuo Z, Kwan P, Baum L. In vitro transport profile of carbamazepine, oxcarbazepine, eslicarbazepine acetate, and their active metabolites by human P-glycoprotein. Epilepsia 2011;52(10):1894–904.
   PubMed Web of Science ®Google Scholar
• Ma A, Wang C, Chen Y, Yuan W. P-glycoprotein alters blood-brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy. Drug Des Dev Ther 2013;7:1447–54.
   PubMed Web of Science ®Google Scholar
• Baltes S, Gastens AM, Fedrowitz M, et al. Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 2007;52(2):333–46.
   PubMed Web of Science ®Google Scholar
• West CL, Mealey KL. Assessment of antiepileptic drugs as substrates for canine P-glycoprotein. Am J Vet Res 2007;68(10):1106–10.
   PubMed Web of Science ®Google Scholar
• Rambeck B, Jürgens UH, May TW, et al. Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy. Epilepsia 2006;47(4):681–94.
   PubMed Web of Science ®Google Scholar
• Potschka H, Fedrowitz M, Löscher W. P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats. Neurosci Lett 2002;327(3):173–6.
   PubMed Web of Science ®Google Scholar
• Weiss J, Kerpen CJ, Lindenmaier H, et al. Interaction of antiepileptic drugs with human P-glycoprotein in vitro. J Pharmacol Exp Ther 2003;307(1):262–7.
   PubMed Web of Science ®Google Scholar
• Zhang C, Chanteux H, Zuo Z, et al. Potential role for human P-glycoprotein in the transport of lacosamide. Epilepsia 2013;54(7):1154–60.
   PubMed Web of Science ®Google Scholar
• Luna-Tortós C, Fedrowitz M, Löscher W. Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology 2008;55(8):1364–75.
   PubMed Web of Science ®Google Scholar
• Potschka H, Baltes S, Löscher W. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res 2004;58(2–3):85–91.
   PubMed Web of Science ®Google Scholar
• Nakanishi H, Yonezawa A, Matsubara K, Yano I. Impact of P-glycoprotein and breast cancer resistance protein on the brain distribution of antiepileptic drugs in knockout mouse models. Eur J Pharmacol 2013;710(1–3):20–8.
   PubMed Web of Science ®Google Scholar
• Luna-Tortós C, Rambeck B, Jürgens UH, Löscher W. The antiepileptic drug topiramate is a substrate for human P-glycoprotein but not multidrug resistance proteins. Pharm Res 2009;26(11):2464–70.
   PubMed Web of Science ®Google Scholar
• Zhang C, Kwan P, Zuo Z, Baum L. In vitro concentration dependent transport of phenytoin and phenobarbital, but not ethosuximide, by human P-glycoprotein. Life Sci 2010;86(23–24):899–905.
   PubMed Web of Science ®Google Scholar
• Xu Y, Zhi F, Xu G, et al. Overcoming multidrug- resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416. Biosci Rep 2012;32:559–66.
   PubMed Web of Science ®Google Scholar
• Verbeek J, Eriksson J, Syvänen S, et al. [11C] phenytoin revisited: synthesis by [11C] CO carbonylation and first evaluation as a P-gp tracer in rats. EJNMMI Res 2012;2:36.
   PubMed Web of Science ®Google Scholar
• Potschka H, Loscher W. In vivo evidence for P-glycoprotein-mediated transport of phenytoin at the blood-brain barrier of rats. Epilepsia 2001;42:1231–40.
   PubMed Web of Science ®Google Scholar
• Marchi N, Guiso G, Rizzi M, et al. A pilot study on brain-to-plasma partition of 10,11-dyhydro-10-hydroxy-5H-dibenzo (b, f) azepine-5-carboxamide and MDR1 brain expression in epilepsy patients not responding to oxcarbazepine. Epilepsia 2005;46:1613–9.
   PubMed Web of Science ®Google Scholar
• Bauer M, Karch R, Zeitlinger M, et al. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology 2014;83:1326–31.
   PubMed Web of Science ®Google Scholar
• Liu JY, Thom M, Catarino CB, et al. Neuropathology of the blood–brain barrier and pharmaco-resistance in human epilepsy. Brain 2012;1:1–19.
   Web of Science ®Google Scholar
• Lazarowski A, Sevlever G, Taratuto A, et al. Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr Neurol 1999;21:731–4.
   PubMed Web of Science ®Google Scholar
• Dombrowski SM, Desai SY, Marroni M, et al. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 2001;42:1501–6.
   PubMed Web of Science ®Google Scholar
• Sisodiya SM, Lin WR, Harding BN, et al. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 2002;125:22–31.
   PubMed Web of Science ®Google Scholar
• Aronica E, Gorter JA, Ramkema M, et al. Expression and cellular distribution of multidrug resistance-related proteins in the hippocampus of patients with mesial temporal lobe epilepsy. Epilepsia 2004;45:441–51.
   PubMed Web of Science ®Google Scholar
• Summers MA, Moore JL, McaAuley JW. Use of verapamil as a potential P-glycoprotein inhibitor in a patient with refractory epilepsy. Ann Pharmacother 2004;38:1631–4.
   PubMed Web of Science ®Google Scholar
• Zhou SF. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica 2008;38:802–32.
   PubMed Web of Science ®Google Scholar
• Baars C, Löscher W, Leeb T, et al. Polymorphic variants of the multidrug resistance gene MDR1a and response to antiepileptic drug treatment in the kindling model of epilepsy. Eur J Pharmacol 2006;550:54–61.
   PubMed Web of Science ®Google Scholar
• Lovrić M, Božina N, Hajnšek S, et al. Association between lamotrigine concentrations and ABCB1 polymorphisms in patients with epilepsy. Ther Drug Monit 2012;34(5):518–25.
   PubMed Web of Science ®Google Scholar
• Löscher W, Klotz U, Zimprich F, Schmidt D. The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia 2009;50:1–23.
   PubMed Web of Science ®Google Scholar
• Siddiqui A, Kerb R, Weale ME, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2003;348:1442–8.
   PubMed Web of Science ®Google Scholar
• Ebid AHI, Ahmed MMM, Mohammed SA. Therapeutic drug monitoring and clinical outcomes in epileptic Egyptian patients: a gene polymorphism perspective study. Ther Drug Monit 2007;29:305–12.
   PubMed Web of Science ®Google Scholar
• Taur SR, Kulkarni NB, Gandhe PP, et al. Association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and activity of P-glycoprotein with response to anti-epileptic drugs. J Postgrad Med 2014;60(3):265–9.
   PubMed Web of Science ®Google Scholar
• Shaheen U, Prasad DK, Sharma V, et al. Significance of MDR1 gene polymorphism C3435T in predicting drug response in epilepsy. Epilepsy Res 2014;108:251–6.
   PubMed Web of Science ®Google Scholar
• Hoffmeyer S, Burk O, von Richter O, et al. Function polymorphisms of the human multidrug–resistance gene: multidrug sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2008;97:3473–8.
   Google Scholar
• Basic S, Hajnsek S, Bozina N, et al. The influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with generalized epilepsy. Seizure Eur J Epilepsy 2008;17:524–30.
   PubMed Web of Science ®Google Scholar
• Kwan P, Wong V, Ng PW, et al. Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese. Pharmacogenomics 2009;10(5):723–32.
   PubMed Web of Science ®Google Scholar
• Kimchi-Sarfaty C, Oh JM, Kim IW, et al. A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 2007;315(5811):525–8.
   PubMed Web of Science ®Google Scholar
• Maleki M, Sayyah M, Kamgarpour F, et al. Association between ABCB1–T1236C polymorphism and drug-resistant epilepsy in Iranian female patients. Iran Biomed J 2010;14:89–96.
   PubMedGoogle Scholar
• Seven M, Batar B, Unal S, et al. The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children. Mol Biol Rep 2014;41(1):331–6.
   PubMed Web of Science ®Google Scholar
• Haerian BS, Lim KS, Tan CT, et al. Association of ABCB1 gene polymorphisms and their haplotypes with response to antiepileptic drugs: a systematic review and meta-analysis. Pharmacogenomics 2011;12(5):713–25.
   PubMed Web of Science ®Google Scholar
• Saad K, Hammad E, Hassan AF, Badry R. Trace element, oxidant, and antioxidant enzyme values in blood of children with refractory epilepsy. Int J Neurosci 2014;124:181–6.
   PubMed Web of Science ®Google Scholar
• Jiang T, Long H, Ma Y, et al. Altered expression of pannexin proteins in patients with temporal lobe epilepsy. Mol Med Rep 2013;8:1801–6.
   PubMed Web of Science ®Google Scholar
• Potschka H. Modulating P-glycoprotein regulation: future perspectives for pharmacoresistant epilepsies? Epilepsia 2010;51:1333–47.
   PubMed Web of Science ®Google Scholar