TY - JOUR
T1 - Pharmacogenetic variants of CYP2C9 and CYP2C19 associated with adverse reactions induced by antiepileptic drugs used in Peru
AU - Alvarado, Angel T.
AU - Muñoz, Ana María
AU - Varela, Nelson
AU - Sullón-Dextre, Luis
AU - Pineda, Mario
AU - Bolarte-Arteaga, Mario
AU - Bendezú, María R.
AU - García, Jorge A.
AU - Chávez, Haydee
AU - Surco-Laos, Felipe
AU - Melgar-Merino, Elizabeth J.
AU - Cuba-Garcia, Pompeyo A.
AU - Molina-Cabrera, Aura
AU - Pari-Olarte, Bertha
AU - Bonifaz-Hernandez, Mario
AU - Panay-Centeno, Juan F.
AU - Kong-Chirinos, José
AU - Almeida-Galindo, José
N1 - Publisher Copyright:
© Alvarado AT et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023
Y1 - 2023
N2 - Epilepsy is the most common neurological disorder with a worldwide incidence of 20% and a treatment failure rate of 25–30%. The fluctuation in serum levels, efficacy and safety of antiepileptic drugs can be attributed to single nucleotide polymorphisms of genes encoding their respective proteins involved in drug metabolism. The present study attempted to evaluate the pharmacogenetic variants of CYP2C9 and CYP2C19 associated with adverse reactions induced by antiepileptic drugs used in Peru. Few studies were found to significantly associate the CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3 single nucleotide polymorphisms with elevated serum levels of valproic acid and carbamazepine, and valproic acid induction of hyperammonemia, and adverse reactions cutaneous for carbamazepine. There is further evidence of a significant association of CYP2C9*2/CYP2C9*3 with severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and epidermal necrolysis (TEN) phenytoin-induced. CYP2C9*3 may be a pharmacogenetic biomarker for such a drug. It is proposed to reduce the dose of drugs for intermediate and poor metabolizers. No pharmacogenetic studies were found in patients with epilepsy in Peruvian populations. It is concluded that this review could help physicians in the prediction and prevention of adverse reactions induced by antiepileptic drugs, as well as to improve their pharmacotherapeutic results. It could also be used as scientific evidence to carry out pharmacogenetic and precision medicine studies in Peruvian patients with epilepsy, due to their tricontinental and Latin American ancestry.
AB - Epilepsy is the most common neurological disorder with a worldwide incidence of 20% and a treatment failure rate of 25–30%. The fluctuation in serum levels, efficacy and safety of antiepileptic drugs can be attributed to single nucleotide polymorphisms of genes encoding their respective proteins involved in drug metabolism. The present study attempted to evaluate the pharmacogenetic variants of CYP2C9 and CYP2C19 associated with adverse reactions induced by antiepileptic drugs used in Peru. Few studies were found to significantly associate the CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3 single nucleotide polymorphisms with elevated serum levels of valproic acid and carbamazepine, and valproic acid induction of hyperammonemia, and adverse reactions cutaneous for carbamazepine. There is further evidence of a significant association of CYP2C9*2/CYP2C9*3 with severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and epidermal necrolysis (TEN) phenytoin-induced. CYP2C9*3 may be a pharmacogenetic biomarker for such a drug. It is proposed to reduce the dose of drugs for intermediate and poor metabolizers. No pharmacogenetic studies were found in patients with epilepsy in Peruvian populations. It is concluded that this review could help physicians in the prediction and prevention of adverse reactions induced by antiepileptic drugs, as well as to improve their pharmacotherapeutic results. It could also be used as scientific evidence to carry out pharmacogenetic and precision medicine studies in Peruvian patients with epilepsy, due to their tricontinental and Latin American ancestry.
KW - Antiepileptic drugs
KW - CYP2C19
KW - CYP2C9
KW - clinical implication
KW - pharmacogenetics
KW - precision medicine
UR - http://www.scopus.com/inward/record.url?scp=85170706020&partnerID=8YFLogxK
U2 - 10.3897/pharmacia.70.e109011
DO - 10.3897/pharmacia.70.e109011
M3 - Artículo de revisión
AN - SCOPUS:85170706020
SN - 0428-0296
VL - 70
SP - 603
EP - 618
JO - Pharmacia
JF - Pharmacia
IS - 3
ER -