|
丙戊酸在治疗儿童癫痫中的安全性研究现况
|
Abstract:
丙戊酸作为一种经典的广谱抗癫痫药,具有多种抗癫痫机制,被广泛的用于治疗几乎所有类型的癫痫及癫痫综合征。尽管大量的研究已证明丙戊酸具有良好的安全性,但因儿童群体有着不同于成人的生理及药物代谢特点,一些药物不良反应,特别是与年龄相关的药物不良反应仍限制了其应用。因此,本文围绕丙戊酸的药理作用、药代谢动力学、儿童药物代谢特点以及成人与儿童药物不良反应的异同来对丙戊酸在治疗儿童癫痫中的安全性作出综述。
Valproic acid (VPA), as a broad-spectrum antiepileptic drug, is widely used in the treatment of almost all types of seizure, epilepsy and epilepsy syndrome due to its multiple mechanisms of action. Although numerous studies suggest the acceptable safety profile of VPA, some adverse drug reactions, especially those age-dependent, limit its application in children as the physiological and drug metabolism characteristics of children are different from adults. Herein, this article reviews the safety of VPA in the treatment of childhood by focusing on its action mechanisms, pharmacokinetics, characteristics of drug metabolism in children and similarities and differences of adverse drug reactions in adults and children.
[1] | Fisher, R.S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J.H., Elger, C.E., et al. (2014) ILAE Official Report: A Practical Clinical Definition of Epilepsy. Epilepsia, 55, 475-482. https://doi.org/10.1111/epi.12550 |
[2] | Löscher, W., Potschka, H., Sisodiya, S.M. and Vezzani, A. (2020) Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacological Reviews, 72, 606-638. https://doi.org/10.1124/pr.120.019539 |
[3] | Mac, T.L., Tran, D., Quet, F., Odermatt, P., Preux, P. and Tan, C.T. (2007) Epidemiology, Aetiology, and Clinical Management of Epilepsy in Asia: A Systematic Review. The Lancet Neurology, 6, 533-543. https://doi.org/10.1016/s1474-4422(07)70127-8 |
[4] | Dennis, M., Spiegler, B.J., Juranek, J.J., Bigler, E.D., Snead, O.C. and Fletcher, J.M. (2013) Age, Plasticity, and Homeostasis in Childhood Brain Disorders. Neuroscience & Biobehavioral Reviews, 37, 2760-2773. https://doi.org/10.1016/j.neubiorev.2013.09.010 |
[5] | Hunter, M.B., Yoong, M., Sumpter, R.E., Verity, K., Shetty, J., McLellan, A., et al. (2019) Neurobehavioral Problems in Children with Early-Onset Epilepsy: A Population-Based Study. Epilepsy & Behavior, 93, 87-93. https://doi.org/10.1016/j.yebeh.2019.01.019 |
[6] | Steriade, C., French, J. and Devinsky, O. (2020) Epilepsy: Key Experimental Therapeutics in Early Clinical Development. Expert Opinion on Investigational Drugs, 29, 373-383. https://doi.org/10.1080/13543784.2020.1743678 |
[7] | Romoli, M., Mazzocchetti, P., D’Alonzo, R., Siliquini, S., Rinaldi, V.E., Verrotti, A., et al. (2019) Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences. Current Neuropharmacology, 17, 926-946. https://doi.org/10.2174/1570159x17666181227165722 |
[8] | Tomson, T., Battino, D. and Perucca, E. (2016) Valproic Acid After Five Decades of Use in Epilepsy: Time to Reconsider the Indications of a Time-Honoured Drug. The Lancet Neurology, 15, 210-218. https://doi.org/10.1016/s1474-4422(15)00314-2 |
[9] | Cofini, M., Quadrozzi, F., Favoriti, P., Favoriti, M. and Cofini, G. (2015) Valproic Acid-Induced Acute Pancreatitis in Pediatric Age: Case Series and Review of Literature. Il Giornale di chirurgia, 36, 158-160. |
[10] | Rinaldi, T., Kulangara, K., Antoniello, K. and Markram, H. (2007) Elevated NMDA Receptor Levels and Enhanced Postsynaptic Long-Term Potentiation Induced by Prenatal Exposure to Valproic Acid. Proceedings of the National Academy of Sciences of the United States of America, 104, 13501-13506. https://doi.org/10.1073/pnas.0704391104 |
[11] | Chateauvieux, S., Morceau, F., Dicato, M. and Diederich, M. (2010) Molecular and Therapeutic Potential and Toxicity of Valproic Acid. Journal of Biomedicine and Biotechnology, 2010, Article ID: 479364. https://doi.org/10.1155/2010/479364 |
[12] | Nalivaeva, N.N., Belyaev, N.D. and Turner, A.J. (2009) Sodium Valproate: An Old Drug with New Roles. Trends in Pharmacological Sciences, 30, 509-514. https://doi.org/10.1016/j.tips.2009.07.002 |
[13] | Ghiglieri, V., Sgobio, C., Patassini, S., Bagetta, V., Fejtova, A., Giampà, C., et al. (2010) TrkB/BDNF-Dependent Striatal Plasticity and Behavior in a Genetic Model of Epilepsy: Modulation by Valproic Acid. Neuropsychopharmacology, 35, 1531-1540. https://doi.org/10.1038/npp.2010.23 |
[14] | 张恩慧, 张鹤声, 陈雨婕, 等. 广谱药物的“广谱”作用: 论丙戊酸在癫痫及共患病中的应用[J]. 癫痫杂志, 2023, 9(5): 393-399. |
[15] | Patsalos, P.N., Zugman, M., Lake, C., James, A., Ratnaraj, N. and Sander, J.W. (2017) Serum Protein Binding of 25 Antiepileptic Drugs in a Routine Clinical Setting: A Comparison of Free Non-Protein‐Bound Concentrations. Epilepsia, 58, 1234-1243. https://doi.org/10.1111/epi.13802 |
[16] | Shen, X., Chen, X., Lu, J., Chen, Q., Li, W., Zhu, J., et al. (2022) Pharmacogenetics-Based Population Pharmacokinetic Analysis and Dose Optimization of Valproic Acid in Chinese Southern Children with Epilepsy: Effect of ABCB1 Gene Polymorphism. Frontiers in Pharmacology, 13, Article 1037239. https://doi.org/10.3389/fphar.2022.1037239 |
[17] | Xu, S., Chen, Y., Zhao, M., Guo, Y., Wang, Z. and Zhao, L. (2018) Population Pharmacokinetics of Valproic Acid in Epileptic Children: Effects of Clinical and Genetic Factors. European Journal of Pharmaceutical Sciences, 122, 170-178. https://doi.org/10.1016/j.ejps.2018.06.033 |
[18] | Kearns, G.L., Abdel-Rahman, S.M., Alander, S.W., Blowey, D.L., Leeder, J.S. and Kauffman, R.E. (2003) Developmental Pharmacology—Drug Disposition, Action, and Therapy in Infants and Children. New England Journal of Medicine, 349, 1157-1167. https://doi.org/10.1056/nejmra035092 |
[19] | Matalová, P., Urbánek, K. and Anzenbacher, P. (2016) Specific Features of Pharmacokinetics in Children. Drug Metabolism Reviews, 48, 70-79. https://doi.org/10.3109/03602532.2015.1135941 |
[20] | van Groen, B.D., Pilla Reddy, V., Badée, J., Olivares‐Morales, A., Johnson, T.N., Nicolaï, J., et al. (2020) Pediatric Pharmacokinetics and Dose Predictions: A Report of a Satellite Meeting to the 10th Juvenile Toxicity Symposium. Clinical and Translational Science, 14, 29-35. https://doi.org/10.1111/cts.12843 |
[21] | Liu, G., Slater, N. and Perkins, A. (2017) Epilepsy: Treatment Options. American Family Physician, 96, 87-96. |
[22] | Shih, J.J., Whitlock, J.B., Chimato, N., Vargas, E., Karceski, S.C. and Frank, R.D. (2017) Epilepsy Treatment in Adults and Adolescents: Expert Opinion, 2016. Epilepsy & Behavior, 69, 186-222. https://doi.org/10.1016/j.yebeh.2016.11.018 |
[23] | Verrotti, A., Striano, P., Iapadre, G., Zagaroli, L., Bonanni, P., Coppola, G., et al. (2018) The Pharmacological Management of Lennox-Gastaut Syndrome and Critical Literature Review. Seizure, 63, 17-25. https://doi.org/10.1016/j.seizure.2018.10.016 |
[24] | Wirrell, E.C., Hood, V., Knupp, K.G., Meskis, M.A., Nabbout, R., Scheffer, I.E., et al. (2022) International Consensus on Diagnosis and Management of Dravet Syndrome. Epilepsia, 63, 1761-1777. https://doi.org/10.1111/epi.17274 |
[25] | Kapur, J., Elm, J., Chamberlain, J.M., Barsan, W., Cloyd, J., Lowenstein, D., et al. (2019) Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. New England Journal of Medicine, 381, 2103-2113. https://doi.org/10.1056/nejmoa1905795 |
[26] | Chamberlain, J.M., Kapur, J., Shinnar, S., Elm, J., Holsti, M., Babcock, L., et al. (2020) Efficacy of Levetiracetam, Fosphenytoin, and Valproate for Established Status Epilepticus by Age Group (ESETT): A Double-Blind, Responsive-Adaptive, Randomised Controlled Trial. The Lancet, 395, 1217-1224. https://doi.org/10.1016/s0140-6736(20)30611-5 |
[27] | Guo, H., Jing, X., Sun, J., Hu, Y., Xu, Z., Ni, M., et al. (2019) Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update. Current Pharmaceutical Design, 25, 343-351. https://doi.org/10.2174/1381612825666190329145428 |
[28] | Perucca, E. (2002) Pharmacological and Therapeutic Properties of Valproate: A Summary after 35 Years of Clinical Experience. CNS Drugs, 16, 695-714. https://doi.org/10.2165/00023210-200216100-00004 |
[29] | Gerstner, T., Büsing, D., Bell, N., Longin, E., Kasper, J., Klostermann, W., et al. (2007) Valproic Acid-Induced Pancreatitis: 16 New Cases and a Review of the Literature. Journal of Gastroenterology, 42, 39-48. https://doi.org/10.1007/s00535-006-1961-4 |
[30] | Bischof, M.C.M., Stadelmann, M.I.E., Janett, S., Bianchetti, M.G., Camozzi, P., Goeggel Simonetti, B., et al. (2023) Valproic Acid-Associated Acute Pancreatitis: Systematic Literature Review. Journal of Clinical Medicine, 12, Article 6044. https://doi.org/10.3390/jcm12186044 |
[31] | Jahromi, S.R., Togha, M., Fesharaki, S.H., Najafi, M., Moghadam, N.B., Kheradmand, J.A., et al. (2011) Gastrointestinal Adverse Effects of Antiepileptic Drugs in Intractable Epileptic Patients. Seizure, 20, 343-346. https://doi.org/10.1016/j.seizure.2010.12.011 |
[32] | Marson, A., Burnside, G., Appleton, R., Smith, D., Leach, J.P., Sills, G., et al. (2021) The SANAD II Study of the Effectiveness and Cost-Effectiveness of Valproate versus Levetiracetam for Newly Diagnosed Generalised and Unclassifiable Epilepsy: An Open-Label, Non-Inferiority, Multicentre, Phase 4, Randomised Controlled Trial. The Lancet, 397, 1375-1386. https://doi.org/10.1016/s0140-6736(21)00246-4 |
[33] | Kılıç, B., Serdaroğlu, E., Polat, B.G., İnce, T., Esenülkü, G., Topçu, Y., et al. (2022) Trends in the Choice of Antiseizure Medications in Juvenile Myoclonic Epilepsy: A Retrospective Multi-Center Study from Turkey between 2010 and 2020. Seizure: European Journal of Epilepsy, 99, 48-53. https://doi.org/10.1016/j.seizure.2022.05.005 |
[34] | Brigo, F. and Igwe, S.C. (2017) Ethosuximide, Sodium Valproate or Lamotrigine for Absence Seizures in Children and Adolescents. Cochrane Database of Systematic Reviews, 2, CD003032. https://doi.org/10.1002/14651858.cd003032.pub3 |
[35] | Silvennoinen, K., de Lange, N., Zagaglia, S., Balestrini, S., Androsova, G., Wassenaar, M., et al. (2019) Comparative Effectiveness of Antiepileptic Drugs in Juvenile Myoclonic Epilepsy. Epilepsia Open, 4, 420-430. https://doi.org/10.1002/epi4.12349 |
[36] | Nanau, R.M. and Neuman, M.G. (2013) Adverse Drug Reactions Induced by Valproic Acid. Clinical Biochemistry, 46, 1323-1338. https://doi.org/10.1016/j.clinbiochem.2013.06.012 |
[37] | Yamamoto, Y., Takahashi, Y., Imai, K., Mishima, N., Yazawa, R., Inoue, K., et al. (2013) Risk Factors for Hyperammonemia in Pediatric Patients with Epilepsy. Epilepsia, 54, 983-989. https://doi.org/10.1111/epi.12125 |
[38] | Zhu, J., Lu, J., Shen, X., He, Y., Xia, H., Li, W., et al. (2023) SCN1A Polymorphisms and Haplotypes Are Associated with Valproic Acid Treatment Outcomes in Chinese Children with Epilepsy. Pediatric Neurology, 146, 55-64. https://doi.org/10.1016/j.pediatrneurol.2023.06.010 |
[39] | Fan, D., Miao, J., Fan, X., Wang, Q. and Sun, M. (2019) Effects of Valproic Acid on Bone Mineral Density and Bone Metabolism: A Meta-Analysis. Seizure, 73, 56-63. https://doi.org/10.1016/j.seizure.2019.10.017 |
[40] | Kumar, R., Vidaurre, J. and Gedela, S. (2019) Valproic Acid-Induced Coagulopathy. Pediatric Neurology, 98, 25-30. https://doi.org/10.1016/j.pediatrneurol.2019.04.019 |
[41] | Gerstner, T., Teich, M., Bell, N., Longin, E., Dempfle, C., Brand, J., et al. (2006) Valproate‐Associated Coagulopathies Are Frequent and Variable in Children. Epilepsia, 47, 1136-1143. https://doi.org/10.1111/j.1528-1167.2006.00587.x |
[42] | Lee, Y.J., Kim, T., Bae, S.H., Kim, Y., Han, J.H., Yun, C., et al. (2013) Levetiracetam Compared with Valproic Acid for the Prevention of Postoperative Seizures after Supratentorial Tumor Surgery: A Retrospective Chart Review. CNS Drugs, 27, 753-759. https://doi.org/10.1007/s40263-013-0094-6 |
[43] | Kaczorowska-Hac, B., Matheisel, A., Maciejka-Kapuscinska, L., Wisniewski, J., Alska, A., Adamkiewicz-Drozynska, E., et al. (2012) Anemia Secondary to Valproic Acid Therapy in a 13-Year-Old Boy: A Case Report. Journal of Medical Case Reports, 6, Article No. 239. https://doi.org/10.1186/1752-1947-6-239 |