PHARMACOGENETIC'S POSITION ON SIDE EFFECTS OF ANTIEPILEPTIC THERAPY IN CHILDREN – WHEN SHOULD PAEDIATRICIAN BE CAREFUL?
Keywords:
children, epilepsy, pharmacogenetics, adverse drug effectsAbstract
It is known that antiepileptic drug therapy can produce many side effects, therefore it requires continued monitoring by doctor, psychologist as well as education of the family members. Recently, modern epileptology focuses itself on pharmacogenetics as pediatric patients tend to have more variable pharmacokinetics and expectancy of side effects than adults. The aim of this article was reviewing relationship between pharmacogenetics and pharmacokinetics of the most frequently used antiepileptic drugs in children (valproate, carbamazepine, levetiracetam, lamotrigine, ethosuximide), by analyzing available scientific works and literature. The authors discussed the everyday clinical paediatric practiceon childrensuffering epilepsy experiencing side effects and unexpected serum drug levels although they were taking their medicines regularly.Suggestion would be to refer them for further pharmacogenetic testingaccording to consultation with neuropediatrician, genetic specialist and metabolism expert. We have found that pharmacogenetics have big impact on paediatric epilepsy treatment, as well aspediatric primary health careplay an important role inadverse drug effects detection.
References
Johnoson TN. Development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children. Toxicology 2003; 192: 37 – 48.
Kearns GL. Pharmacogenetics and development: are infants and children at increased risk for adverse outcomes?Curr Opin Pediatr. 1995;7(2):220-233.
Dodson WE. Special pharmacokinetic considerations in children. Epilepsia. 1987;28: 56-70.
López-García M.A, et al. Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy. Pharmacological reports 2017; 69:73.
Buck L.M. Precision Medicine in Children: a Review of the Recent Literature. Pediatric pharmacotherapy 2017; 23:2.
Zhu M, Li H, Shi L, Chen P, Luo J, Zhang Z. The pharmacogenomics of valproate acid. Journal of Human Genetics 2017;62:1009–1014.
Xu S, Chen Y, Zhao M, Guo Y, Wang Z, Zhao L. Population pharmacokinetics of valproic acid in epileptic children: Effects of clinical and genetic factors. European Journal of Pharmaceutical Sciences 2018; 122:170-178.
Mei Sh et al. Genetic polymorphisms and valproic acid plasma concentration in children with epilepsy on valproic acid monotherapy. European Journal of Epilepsy 2017; 51:22-26.
Milovanović D, et al. The influence of CYP2C8'3 on carbamazepine serum concentration in epileptic pediatric patients. BMJG 2016; 19(1):21-28.
Đorđević N, Janković M.S, Milovanović R.S. Pharmacokinetics and Pharmacogenetics of Carbamazepine in Children.Eur J Drug Metab Pharmacokinet. 2017 Oct;42(5):729-744.
Đorđević N, Milovanović DD, Radovanović M, et al. CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy. Eur J Clin Pharmacol. 2016;72(4):439–445.
Y Chen, et al. A Population Pharmacokinetic-Pharmacogenetic Model of Lamotrigine in Chinese Children With Epilepsy. The Drug Monit 2018; 40(6):730-737
Agrawal A, Bamergee A. A Review on Pharmacokinetics of Levetiracetam in Neonates. Current Drug Metabolism 2017; 18: 727-734
Dilena R, Striano P, Traverso M, et al. Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation. Brain & Development 2015;
Pisano T, Numis L.A, Heavin B.S, et al, Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 2015; 1-7
Holland K, O'Brien P.V, Keddache M, et al. Pharmacogenetics of Antiepileptic Drug Efficacy in Childhood Absence Epilepsy. ANN NEUROL 2017;81:444–453
