Background: Paroxetine is a selective serotonin reuptake inhibitor metabolized by cytochrome P450 (CYP)2D6. Only small-scale studies have reported the impact of CYP2D6 genotype on paroxetine exposure, and international guidelines differ in their recommendations on whether paroxetine should be administered according to CYP2D6 genotype. To clarify this issue, the aim of the present study was to investigate the impact of CYP2D6 genotype on paroxetine serum concentration in a large population of patients after adjusting for CYP2C19 genotype, age, and sex.
Methods: Patients from a therapeutic drug monitoring database with records on their paroxetine serum concentrations and CYP2D6 and CYP2C19 genotyping between 2010 and 2021 were included in the study. The impact of CYP2D6 and CYP2C19 genotypes, age, and sex on the paroxetine concentration-to-dose (C/D) ratio was investigated by multiple linear regression analysis. Patients treated with relevant CYP inhibitors or inducers were excluded.
Results: In total, 304 patients were included in the study: 17 CYP2D6 poor metabolizers (PMs), 114 intermediate metabolizers (IMs), 168 extensive metabolizers (EMs), and 5 ultrarapid metabolizers. Multiple linear regression analysis showed that CYP2D6 IMs and PMs had 2.2-fold and 3.8-fold higher paroxetine C/D-ratios than extensive metabolizers, respectively ( P < 0.001). Patients who were CYP2C19 IMs (n = 70) or PMs (n = 13) had 1.6-fold higher paroxetine C/D ratio than extensive metabolizers ( P = 0.04). An age ≥65 years was associated with a 2.9-fold increased C/D ratio ( P < 0.001), whereas sex was not significantly associated with paroxetine exposure.
Conclusions: The present study showed that CYP2D6 genotype is of significant importance for paroxetine dose adjustments. For CYP2D6 PMs, 25% of the regular paroxetine starting dose may be sufficient, whereas CYP2D6 IMs could receive 50% of the regular dosage. This well-powered study shows that the guidelines should consider the importance of CYP2D6 genotype for personalized dosing of paroxetine.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/FTD.0000000000001096 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Influence of Genetic Polymorphisms in Cytochrome P450 (CYP1A1 and 2D6) Gene on the Susceptibility to Philadelphia Negative Chronic Myeloid Leukemia in Sudanese Patients.
Int J Mol Sci
December 2024
School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK.
The most frequent type of leukemia in Africa is chronic myeloid leukemia (CML). The genetic background of the rarer Philadelphia chromosome (Ph) Ph-ve (BCR-ABL-ve) subform of CML is largely unknown in African patients. Therefore, in this study, we aimed to investigate the role of CYP1A1 and 2D6 SNPs in the pathogenesis of Ph-ve CML in the Sudanese population.
View Article and Find Full Text PDFEvaluation of machine learning algorithms and computational structural validation of CYP2D6 in predicting the therapeutic response to tamoxifen in breast cancer.
Eur Rev Med Pharmacol Sci
December 2024
Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Kingdom of Bahrain.
Objective: CYP2D6 plays a critical role in metabolizing tamoxifen into its active metabolite, endoxifen, which is crucial for its therapeutic effect in estrogen receptor-positive breast cancer. Single nucleotide polymorphisms (SNPs) in the CYP2D6 gene can affect enzyme activity and thus impact tamoxifen efficacy. This study aimed to use machine learning algorithms (MLAs) to identify significant predictors of Breast Cancer-Free Interval (BCFI) and to apply bioinformatics tools to investigate the structural and functional implications of CYP2D6 SNPs.
View Article and Find Full Text PDFUse of a Personalized Clinical Decision Support System for Dosing in Psychopharmacotherapy in Patients with Alcoholic Hallucinosis Based on Pharmacogenomic Markers.
Psychopharmacol Bull
January 2025
Sychev, corresponding member of the Academy of Sciences of Russia, MD, PhD, MD, professor, rector, head of clinical pharmacology and therapy department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.
Introduction: Alcoholic hallucinosis (AH) is one of the severe complications of chronic alcoholism, characterized by psychotic symptoms such as auditory hallucinations and delusions. Haloperidol is widely used to treat AH; however, its therapy is often complicated by side effects. A personalized approach using pharmacogenetic testing (particularly the CYP2D6 polymorphism) allows individualization of haloperidol dosage, improving both safety and efficacy of therapy.
View Article and Find Full Text PDFSchizophrenia is a multifaceted psychiatric disorder characterized by hallucinations, delusions, cognitive impairments, and behavioral disturbances. Genetic factors significantly contribute to its pathogenesis, accounting for approximately 80% of the heritability. Globally, about 1% of the population is affected by schizophrenia, with 45,054 individuals in Kazakhstan receiving medical treatment for the condition, indicating a prevalence rate of 238,6 per 100,000 people.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!