ArticleOmics : a journal of integrative biology2013
Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.
Article in Omics : a journal of integrative biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pharmacogenomic markers associated with drug-induced QT prolongation: a systematic review.PharmacogenomicsPooled it
- Genetic polymorphisms in the opioid receptor delta 1 (OPRD1) gene are associated with methadone dose in methadone maintenance treatment for heroin dependence.Journal of human genetics · 2020Trial
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.International journal of molecular sciences · 2022Article
- Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition.British journal of clinical pharmacology · 2022Article
- Association of the D-amino acid oxidase gene with methadone dose in heroin dependent patients under methadone maintenance treatment.Journal of human genetics · 2022Article
- Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children.CPT: pharmacometrics & systems pharmacology · 2021Article
- Risk Assessment for Heroin Use and Craving Score Using Polygenic Risk Score.Journal of personalized medicine · 2021Article
- Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use.Bosnian journal of basic medical sciences · 2021Review
- Tackling Current Biomedical Challenges With Frontier Biofabrication and Organ-On-A-Chip Technologies.Frontiers in bioengineering and biotechnology · 2021Review
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
- Genetic variants in NECTIN4 encoding an adhesion molecule are associated with continued opioid use.PloS one · 2020Article
- GRK5 Is Associated with the Regulation of Methadone Dosage in Heroin Dependence.The international journal of neuropsychopharmacology · 2018Article
- Effects of cytochrome P450 single nucleotide polymorphisms on methadone metabolism and pharmacodynamics.Biochemical pharmacology · 2018Review
- Pharmacogenetics of Opioid Use Disorder Treatment.CNS drugs · 2018Review
- Pharmacogenetics of Methadone Response.Molecular diagnosis & therapy · 2018Review
- Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.The American journal of drug and alcohol abuse · 2018Article
- Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome.PloS one · 2017Article
- Article
- A Possible Mechanistic Link Between the CYP2C19 Genotype, the Methadone Metabolite Ethylidene-1,5-Dimethyl-3,3-Diphenylpyrrolidene (EDDP), and Methadone-Induced Corrected QT Interval Prolongation in a Pilot Study.Molecular diagnosis & therapy · 2015Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.
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