Process of Personalized Prescription of Valproic Acid as the Main Element of the Management of Epilepsy

Elena N. Bochanova, PhD; Natalia A. Shnayder, PhD, SciD*; Diana D. Dmitrenko, PhD, SciD; Ivan P. Artyukhov, PhD, SciD; Sergey D. Gusev, PhD; Elena A. Yurjeva, PhD; Olga S. Shilkina, MD

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk, the Russian Federation

*Corresponding authorProf. Natalia A. Shnayder, PhD, ScD; Head of the Neurological Center of Epileptology, Neurogenetics and Brain Research of the University Clinic of Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky. Krasnoyarsk, the Russian Federation.  E-mail: nataliashnayder@gmail.com

Published: March 15, 2018.  doi: 10.21103/Article8(1)_OA3

Abstract: 

The purpose of this study was to develop a sequential process of personalized valproic acid (VPA) prescription in patients with epilepsy.
Materials and Methods: We randomly selected 167 patients with epilepsy receiving VPA, based on carriage of CYP2C9*2 and/or CYP2C9*3 and therapeutic drug monitoring. The patients’ CYP2C9 status was determined by CYP2C9 genotyping before the beginning of anticonvulsant therapy.
Results: The sequence of personalized valproic acid prescription has been developed.
Conclusion: Using the sequential process of personalized VPA prescription will allow neurologists, psychiatrists and general practitioners to select starting and maintenance dosages of VPA with respect to the individual patient’s pharmacogenetic profile and thereby, significantly improve the safety of pharmacotherapy in epilepsy patients.

Keywords: 
epilepsy ● CYP2C9 ● valproic acid ● pharmacogenetics ● pharmacokinetics
References: 
  1. Dmitrenko D, Shnayder N, Bochanova E, Artyukhov I, Zyryanov S, Veselova O, et al. [Therapeutic drug monitoring in the treatment of epilepsy]. Vrach (The Doctor). 2017;1:81-83. [Article in Russian].
  2. Shnayder NA, Pilyugina MS, Dmitrenko DV, Bochanova EN, Shapovalova EA, Erikalova SA, et al. Pharmacogenetics of valproic acid as unmodified risk factor of adverse drug reactions. Medical and Health Science Journal. 2011; 7: 26-38.
  3. Shnaider NA, Sychev DA, Pilyugina MS, Dmitrenko DV, Bochanova EN, Shapovalova EA. Importance of the pharmacokinetics of valproic acid in an individualized approach to the treatment of epileptic women of fertile age. Neuroscience and Behavioral Physiology. 2012;42(9):963-968. https://doi.org/10.1007/s11055-012-9663-2
  4. Okulova LP. Pedagogical ergonomics: Monograph. Moskow – Ijevsk: Institute of Computer Research; 2011. [In Russian].
  5. Parondjanov VD. Learn to write, read and understand algorithms. Algorithms for the thinking. Fundamentals of algorithmization. Moscow: DMK Press; 2012.  [In Russian].
  6. Kiang TK, Ho PC, Anari MR, Tong V, Abbott FS, Chang TK. Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype. Toxicol. Sci. 2006;94(2):261-71.
  7. Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther. 2014;96(5):542-8. doi: 10.1038/clpt.2014.159.
  8. Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Drugs metabolism. The scientific basis of personalized medicine. M. GEOTAR-Media; 2008. [in Russian].
  9. Ho PC, Abbott FS, Zanger UM, Chang TK. Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes. Pharmacogenomics J. 2003;3(6):335-42.
  10. Brusturean-Bota ES, Trifa AP, Coadă CA, Buzoianu AD, Perju-Dumbravă L..Impact of CYP2C9 genetic polymorphisms on valproate dosage, plasma concentrations of valproate and clinical response to valproate. HVM Bioflux. 2013;5(3):94-8.
  11. Tan L, Yu JT, Sun YP, Ou JR, Song JH, Yu Y. The influence of cytochrome oxidase CYP2A6, CYP2B6, and CYP2C9 polymorphisms on the plasma concentrations of valproic acid in epileptic patients. Clin Neurol Neurosurg. 2010;112(4):320-3. doi: 10.1016/j.clineuro.2010.01.002.
  12. LoVecchio F, Shriki J, Samaddar R. L-carnitine was safely administered in the setting of valproate toxicity. Am J Emerg Med. 2005;23(3):321-2.
  13. Blackford MG, Do ST, Enlow TC, Reed MD. Valproic Acid and topiramate induced hyperammonemic encephalopathy in a patient with normal serum carnitine. J Pediatr Pharmacol Ther. 2013;18(2):128-36. doi: 10.5863/1551-6776-18.2.128.
  14. Mojumder DK, De Oleo RR. Differential ammonia decay kinetics indicates more than one concurrent etiological mechanism for symptomatic hyperammonemia caused by valproate overdose. Indian J Pharmacol. 2014; 46(3):345-7. doi: 10.4103/0253-7613.132200.
  15. Rousseau MC, Montana M, Villano P, Catala A, Blaya J, Valkov M, et al. Valproic acid-induced encephalopathy in very long course treated patients. Brain Inj. 2009;23(12):981-4. doi: 10.3109/02699050903302344.
  16. Bűdi T, Tóth K, Nagy A, Szever Z, Kiss Á, Temesvári M, et al. Clinical significance of CYP2C9-status guided valproic acid therapy in children. Epilepsia. 2015; 56(6):849-55. doi: 10.1111/epi.13011.

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International Journal of Biomedicine. 2018;8(1):26-32. ©2018 International Medical Research and Development Corporation. All rights reserved.