ArticleThe pharmacogenomics journal2013
Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms.
Article in The pharmacogenomics journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Movement disorders associated with antiseizure medications: A systematic review.Epilepsy & behavior : E&B · 2022Pooled it
- Drug-induced cerebellar ataxia: a systematic review.CNS drugs · 2014Pooled it
- Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing.Clinical pharmacology and therapeutics · 2014Guideline
- Association BetweenPharmaceuticals (Basel, Switzerland) · 2025Article
- Role of pharmacogenomics for prevention of hypersensitivity reactions induced by aromatic antiseizure medications.Frontiers in pharmacology · 2025Review
- Exome sequencing allows detection of relevant pharmacogenetic variants in epileptic patients.The pharmacogenomics journal · 2022Article
- Frequency ofJournal of personalized medicine · 2022Article
- Pharmacogenetics in Primary Headache Disorders.Frontiers in pharmacology · 2021Review
- A Review of the Important Role ofGenes · 2020Review
- Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin-Induced Cutaneous Adverse Drug Reactions.Clinical and translational science · 2020Article
- Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system.Pharmacogenetics and genomics · 2019Article
- Study of the allelic variants CYP2C9*2 and CYP2C9*3 in samples of the Peruvian mestizo populationBiomedica : revista del Instituto Nacional de Salud · 2019Observational
- Pharmacogenomics of CYP2C9: Functional and Clinical Considerations.Journal of personalized medicine · 2017Review
- Role of CYP2C9, CYP2C19 and EPHX Polymorphism in the Pharmacokinetic of Phenytoin: A Study on Uruguayan Caucasian Subjects.Pharmaceuticals (Basel, Switzerland) · 2017Article
- CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.The pharmacogenomics journal · 2016Article
- Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.The pharmacogenomics journal · 2016Review
- Pharmacogenetics of drug-metabolizing enzymes in US Hispanics.Drug metabolism and personalized therapy · 2015Review
- Independent predictors of delay in emergence from general anesthesia.Anesthesia progress · 2015Article
- Interethnic differences in the relevance of CYP2C9 genotype and environmental factors for diclofenac metabolism in Hispanics from Cuba and Spain.The pharmacogenomics journal · 2014Article
- Psychotropic drug-drug interactions involving P-glycoprotein.CNS drugs · 2012Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacogenetic studies have shown that genetic defects in drug-metabolizing enzymes encoded by CYP2C9, CYP2C19 genes and by the transporter ABCB1 gene can influence phenytoin (PTH) plasma levels and toxicity. The patient reported here is a 2-year-old girl with a medical history of cryptogenic (probably symptomatic) epilepsy, who had her first focal seizure with secondary generalization at 13 months of age. She initially received oral valproate treatment and three months later, she was prescribed an oral oxcarbazepine treatment. At 20 months of age, she was admitted to the Emergency Department because of generalized convulsive Status Epilepticus needing to be immediately treated with rectal diazepam (0.5 mg kg(-1)), intravenous diazepam (0.3 mg kg(-1)), and intravenous phenytoin with an initial-loading dose of 15 mg kg(-1). However, two hours after the initial-loading dose of PTH, the patient developed dizziness, nystagmus, ataxia and excessive sedation. Other potential causes of PTH toxicity were excluded such as drug interactions, decreased albumin or lab error. Therefore, to explain the neurological toxicity, PTH plasma levels and CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms were analyzed. Initial plasma PTH levels were higher than expected (69 mg l(-1); normal range: 10-20 mg l(-1)), and the patient was homozygous for the CYP2C9*2 allele, heterozygous for the CYP2C19*4 allele and homozygous for the 3435C and 1236C ABCB1 alleles. Present findings support the previously established relationship between CYP2C9 and CYP2C19 genetic polymorphisms and the increased risk to develop PTH toxicity owing to high plasma concentrations. Nevertheless, although the association of these genes with PTH-induced adverse effects has been well-documented in adult populations, this is the first report examining the influence of these genetic polymorphisms on PTH plasma levels and toxicity in a pediatric patient.
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