抗癲癇藥物對腎功能損傷的研究進展_Journal of Epilepsy

Authors：

蔡夢婷 ,  丁美萍

浙江大學醫學院附屬第二醫院神經內科（杭州 310009）;

Corresponding?author：

丁美萍, Email: meipingd@163.com

Keywords：

抗癲癇藥物; 腎功能; 不良反應

DOI：

10.7507/2096-0247.20210007

Video：

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癲癇是神經科常見的慢性致殘性疾病，目前主要依賴藥物治療。抗癲癇藥物（AEDs）對肝功能、內分泌系統等的常見不良反應已受到普遍重視，但其對腎功能的影響卻容易被忽視。本文總結了目前常用的 AEDs 的藥物動力學特點及其與腎功能的聯系，包括經典的一代藥物（丙戊酸、卡馬西平）、二代藥物（左乙拉西坦、拉莫三嗪、托吡酯、奧卡西平）以及三代新型藥物（拉考沙胺、吡侖帕奈）。AEDs 引起的腎功能損傷的可分為劑量依賴性和免疫相關非劑量依賴性，前者與腎臟細胞直接毒性損傷或內分泌代謝異常有關，包括 Fanconi 綜合征、低鈉血癥、低鉀血癥、代謝性酸中毒等，一代 AEDs、托吡酯等；后者主要指 AEDs 高敏感綜合征，常見于卡馬西平和拉莫三嗪。用藥方案個體化及早期監測是避免腎功能損傷的關鍵，生物利用度完全且穩定、長半衰期較短、線性藥代動力學特征、蛋白結合率低、肝酶誘導作用少、低代謝產物活性 AEDs 安全性更高、有效性更佳。

Citation： 蔡夢婷, 丁美萍. 抗癲癇藥物對腎功能損傷的研究進展. Journal of Epilepsy, 2021, 7(1): 44-48. doi: 10.7507/2096-0247.20210007 Copy

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3.	Anderson GD, Hakimian S. Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment. Clinical pharmacokinetics, 2014, 53(1): 29-49.
4.	Títoff V, Moury HN, Títoff IB, et al. Seizures, antiepileptic drugs, and CKD. American Journal of Kidney Diseases, 2019, 73(1): 90-101.
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8.	Dedinska I, Manka V, Sagova I, et al. Hyponatremia-carbamazepine medication complications]. Vnitr Lek, 2012, 58(1): 72-75.
9.	Aksoy D, Cevik B, Kurt S, et al. Hypokalemia and hypomagnesaemia related to levetiracetam use. J Clin Neurosci, 2014, 21(11): 1989-1990.
10.	Dell'Orto VG, Belotti EA, Goeggel-Simonetti B, et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol, 2014, 77(6): 958-964.
11.	Bloch KM, Sills GJ, Pirmohamed M, et al. Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics, 2014, 15(6): 857-868.
12.	Lakhoua G, Aouinti I, Sahnoun R, et al. A hemophagocytosis syndrome attributed to phenobarbital. Presse Med, 2016, 45(3): 379-381.
13.	Brix Finnerup N, Hein Sindrup S, Staehelin Jensen T. Management of painful neuropathies. Handb Clin Neurol, 2013, 115: 279-290.
14.	Asconapé JJ. Use of antiepileptic drugs in hepatic and renal disease//Handbook of Clinical Neurology. Elsevier, 2014, 119: 417-432.
15.	Heidari R, Jafari F, Khodaei F, et al. The mechanism of valproic acid-induced fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. Nephrology (Carlton), 2017, 23(4): 351-361.
16.	Knights M, Thekkekkara T, Morris A, et al. Sodium valproate-induced Fanconi type proximal renal tubular acidosis. BMJ Case Rep, 2016: bcr2015213418.
17.	Patel SM, Graff-Radford J, Wieland ML. Valproate-induced fanconi syndrome in a 27-year-old woman. Journal of General Internal Medicine, 2011, 26(9): 1072.
18.	Bansal AD, Hill CE, Berns JS. Use of antiepileptic drugs in patients with chronic kidney disease and end stage renal disease. Semin Dial, 2015, 28(4): 404-412.
19.	de Braganca AC, Moyses ZP, Magaldi AJ. Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression. Nephrol Dial Transplant, 2010, 25(12): 3840-3845.
20.	Rodríguez KAM, Benbadis SR. Managing antiepileptic medication in dialysis patients. Current Treatment Options in Neurology, 2018, 20(11): 45.
21.	Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol, 2009, 41(1): 57-58.
22.	Spengler DC, Montouris GD, Hohler AD. Levetiracetam as a possible contributor to acute kidney injury. Clin Ther, 2014, 36(8): 1303-1306.
23.	Kolomeyer AM, Kodati S. Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical cogan syndrome. Eur J Ophthalmol, 2015, 26(1): e14-16.
24.	Matta A, Assalie NA, Gupta RK, et al. A rare case of lamotrigine-induced acute interstitial nephritis. J Community Hosp Intern Med Perspect, 2016, 6(6): 32976.
25.	Manitpisitkul P, Curtin CR, Shalayda K, et al. Pharmacokinetics of topiramate in patients with renal impairment, end-stage renal disease undergoing hemodialysis, or hepatic impairment. Epilepsy Res, 2014, 108(5): 891-901.
26.	Peltola J, Holtkamp M, Rocamora R, et al. Practical guidance and considerations for transitioning patients from oxcarbazepine or carbamazepine to eslicarbazepine acetate-expert opinion. Epilepsy Behav, 2015, 50: 46-49.
27.	Rolnitsky A, Merlob P, Klinger G. In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia. Pediatr Neurol, 2013, 48(6): 466-468.
28.	De Biase S, Valente M, Gigli GL, et al. Pharmacokinetic drug evaluation of lacosamide for the treatment of partial-onset seizures. Expert Opinion on Drug Metabolism & Toxicology, 2017, 13(9): 997-1005.
29.	Cawello W, Fuhr U, Hering U, et al. Impact of impaired renal function on the pharmacokinetics of the anti-epileptic drug lacosamide. Clin Pharmacokinet, 2013, 52(10): 897-906.
30.	Hamed SA. The effect of antiepileptic drugs on the kidney function and structure. Expert Review of Clinical Pharmacology, 2017, 10(9): 993-1006.
31.	Cawello W, Stockis A, Andreas JO, et al. Advances in epilepsy treatment: lacosamide pharmacokinetic profile: lacosamide pharmacokinetics. Ann N Y Acad Sci, 2014, 1329: 18-32.
32.	Li J, Sun M, Wang X. The adverse-effect profile of lacosamide. Expert Opinion on Drug Safety, 2020, 19(2): 131-138.
33.	Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand, 2013, 127(Suppl 197): 19-24.
34.	Franco V, Crema F, Iudice A, et al. Novel treatment options for epilepsy: focus on perampanel. Pharmacol Res, 2013, 70(1): 35-40.
35.	Hanada T, Hashizume Y, Tokuhara N, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia, 2011, 52(7): 1331-1340.

1. 中國抗癲癇協會. 臨床診療指南: 癲癇病分冊(2015 年修訂版). 人民衛生出版社, 2015: 11.
2. Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. The Lancet, 2019, 393(10172): 689-701.
3. Anderson GD, Hakimian S. Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment. Clinical pharmacokinetics, 2014, 53(1): 29-49.
4. Títoff V, Moury HN, Títoff IB, et al. Seizures, antiepileptic drugs, and CKD. American Journal of Kidney Diseases, 2019, 73(1): 90-101.
5. Ghane Shahrbaf F, Assadi F. Drug-induced renal disorders. J Renal Inj Prev, 2015, 4(3): 57-60.
6. Knights M, Thekkekkara T, Morris A, et al. Sodium valproate induced fanconi type proximal renal tubular acidosis: A case series. In: Pediatric Nephrology, 2015, 30: 1567-1567.
7. Gupta E, Kunjal R, Cury JD. Severe hyponatremia due to valproic acid toxicity. J Clin Med Res, 2015, 7(9): 717-719.
8. Dedinska I, Manka V, Sagova I, et al. Hyponatremia-carbamazepine medication complications]. Vnitr Lek, 2012, 58(1): 72-75.
9. Aksoy D, Cevik B, Kurt S, et al. Hypokalemia and hypomagnesaemia related to levetiracetam use. J Clin Neurosci, 2014, 21(11): 1989-1990.
10. Dell'Orto VG, Belotti EA, Goeggel-Simonetti B, et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol, 2014, 77(6): 958-964.
11. Bloch KM, Sills GJ, Pirmohamed M, et al. Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics, 2014, 15(6): 857-868.
12. Lakhoua G, Aouinti I, Sahnoun R, et al. A hemophagocytosis syndrome attributed to phenobarbital. Presse Med, 2016, 45(3): 379-381.
13. Brix Finnerup N, Hein Sindrup S, Staehelin Jensen T. Management of painful neuropathies. Handb Clin Neurol, 2013, 115: 279-290.
14. Asconapé JJ. Use of antiepileptic drugs in hepatic and renal disease//Handbook of Clinical Neurology. Elsevier, 2014, 119: 417-432.
15. Heidari R, Jafari F, Khodaei F, et al. The mechanism of valproic acid-induced fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. Nephrology (Carlton), 2017, 23(4): 351-361.
16. Knights M, Thekkekkara T, Morris A, et al. Sodium valproate-induced Fanconi type proximal renal tubular acidosis. BMJ Case Rep, 2016: bcr2015213418.
17. Patel SM, Graff-Radford J, Wieland ML. Valproate-induced fanconi syndrome in a 27-year-old woman. Journal of General Internal Medicine, 2011, 26(9): 1072.
18. Bansal AD, Hill CE, Berns JS. Use of antiepileptic drugs in patients with chronic kidney disease and end stage renal disease. Semin Dial, 2015, 28(4): 404-412.
19. de Braganca AC, Moyses ZP, Magaldi AJ. Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression. Nephrol Dial Transplant, 2010, 25(12): 3840-3845.
20. Rodríguez KAM, Benbadis SR. Managing antiepileptic medication in dialysis patients. Current Treatment Options in Neurology, 2018, 20(11): 45.
21. Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol, 2009, 41(1): 57-58.
22. Spengler DC, Montouris GD, Hohler AD. Levetiracetam as a possible contributor to acute kidney injury. Clin Ther, 2014, 36(8): 1303-1306.
23. Kolomeyer AM, Kodati S. Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical cogan syndrome. Eur J Ophthalmol, 2015, 26(1): e14-16.
24. Matta A, Assalie NA, Gupta RK, et al. A rare case of lamotrigine-induced acute interstitial nephritis. J Community Hosp Intern Med Perspect, 2016, 6(6): 32976.
25. Manitpisitkul P, Curtin CR, Shalayda K, et al. Pharmacokinetics of topiramate in patients with renal impairment, end-stage renal disease undergoing hemodialysis, or hepatic impairment. Epilepsy Res, 2014, 108(5): 891-901.
26. Peltola J, Holtkamp M, Rocamora R, et al. Practical guidance and considerations for transitioning patients from oxcarbazepine or carbamazepine to eslicarbazepine acetate-expert opinion. Epilepsy Behav, 2015, 50: 46-49.
27. Rolnitsky A, Merlob P, Klinger G. In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia. Pediatr Neurol, 2013, 48(6): 466-468.
28. De Biase S, Valente M, Gigli GL, et al. Pharmacokinetic drug evaluation of lacosamide for the treatment of partial-onset seizures. Expert Opinion on Drug Metabolism & Toxicology, 2017, 13(9): 997-1005.
29. Cawello W, Fuhr U, Hering U, et al. Impact of impaired renal function on the pharmacokinetics of the anti-epileptic drug lacosamide. Clin Pharmacokinet, 2013, 52(10): 897-906.
30. Hamed SA. The effect of antiepileptic drugs on the kidney function and structure. Expert Review of Clinical Pharmacology, 2017, 10(9): 993-1006.
31. Cawello W, Stockis A, Andreas JO, et al. Advances in epilepsy treatment: lacosamide pharmacokinetic profile: lacosamide pharmacokinetics. Ann N Y Acad Sci, 2014, 1329: 18-32.
32. Li J, Sun M, Wang X. The adverse-effect profile of lacosamide. Expert Opinion on Drug Safety, 2020, 19(2): 131-138.
33. Rogawski MA, Hanada T. Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand, 2013, 127(Suppl 197): 19-24.
34. Franco V, Crema F, Iudice A, et al. Novel treatment options for epilepsy: focus on perampanel. Pharmacol Res, 2013, 70(1): 35-40.
35. Hanada T, Hashizume Y, Tokuhara N, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia, 2011, 52(7): 1331-1340.

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抗癲癇藥物對腎功能損傷的研究進展

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