ArticleScientific reports2021
Relationship between CYP2D6 genotype, activity score and phenotype in a pediatric Thai population treated with risperidone.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 18 citations in OpenAlex.
- The distinct effects of metabolic syndrome on negative symptoms and on antipsychotic therapy of schizophrenia involve insular volume, functional connectivity, and genetic polymorphisms.Translational psychiatry · 2026Article
- Phenoconversion andHepatology forum · 2025Review
- The Frequency of CYP2D6 and CYP3A4/5 Genotypes and The Impact of Their Allele Translation and Phenoconversion-Predicted Enzyme Activity on Risperidone Pharmacokinetics in Saudi Children with Autism.Biochemical genetics · 2024Article
- Into a Deeper Understanding of CYP2D6's Role in Risperidone Monotherapy and the Potential Side Effects in Schizophrenia Spectrum Disorders.International journal of molecular sciences · 2024Article
- Article
- Risperidone plasma level, and its correlation with CYP2D6 gene polymorphism, clinical response and side effects in chronic schizophrenia patients.BMC psychiatry · 2024Article
- Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism.Frontiers in pharmacology · 2024Article
- Pharmacogenetic Variants Associated with Fluoxetine Pharmacokinetics from a Bioequivalence Study in Healthy Subjects.Journal of personalized medicine · 2023Article
- Pharmacogenomics and non-genetic factors affecting drug response in autism spectrum disorder in Thai and other populations: current evidence and future implications.Frontiers in pharmacology · 2023Review
- Introduction of new alternative pipeline using multiplexed fast COLD‑PCR together with sequencing approach highlighting pharmacoeconomics by detection ofBiomedical reports · 2022Article
- Categorization of Cytochrome P4502D6 Activity Score by Urinary Amphetamine/Methamphetamine Ratios.Metabolites · 2022Article
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, the Clinical Pharmacogenetics Implementation Consortium (CPIC) have revised recommendations for the translation of CYP2D6 genotype to phenotype. Changes affect phenotype grouping, as well as the value used to calculate activity score for the CYP2D6*10 allele to better reflect the substantially decreased activity of this allele which is the most frequent allele found in Asian populations. This study aimed to evaluate whether the lower value for CYP2D6*10 as recommended, and the revised phenotype groupings improve the relationship between CYP2D6 genotype and risperidone measures. One hundred and ninety-nine children and adolescents with autism treated with a risperidone-based regimen for at least four weeks were included. CYP2D6 genotype was determined using the Luminex xTAG CYP2D6 Kit assay and translated into phenotype using different translation methods. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Plasma levels of risperidone, risperidone concentration/dose ratio, and risperidone/9-hydroxyrisperidone ratio in patients with an activity score < 1 were significantly higher than those ≥ 1 (P value < 0.001 for all three parameters). Plasma risperidone levels and risperidone concentration/dose ratios were significantly higher in intermediate metabolizers (defined as AS = 0.25-0.75) than normal metabolizer (defined as AS = 1-2) patients (1.44 vs. 0.23 ng/ml, P < 0.001 and 1.63 vs. 0.29 ng/ml/ng, P < 0.001, respectively) as well as risperidone/9-hydroxyrisperidone ratio (0.20 vs. 0.04, P < 0.001). This is the first study in an Asian population utilizing the revised CPIC-recommended method for translating the CYP2D6 genotype to phenotype. In addition to validating that CYP2D6 genetic variation significantly impacts risperidone metabolism, we demonstrated that revised value for the CYP2D6*10 was superior for genotype to phenotype translation. However, at least for risperidone, subjects with an activity score of 1 presented as phenotypic normal, and not intermediate metabolizers, suggesting that phenotype classification is substrate dependent.
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