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Background: The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study.
Methods: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018.
Results: Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events.
Conclusions: CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.
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http://dx.doi.org/10.1055/a-0792-1340 | DOI Listing |
J Clin Pharmacol
September 2025
School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Endoxifen is the most active metabolite of tamoxifen and plays a central role in its therapeutic efficacy. However, significant interindividual variability in endoxifen plasma concentrations, driven by both genetic and non-genetic factors, may result in subtherapeutic exposure for a substantial subset of patients. This study evaluated the influence of CYP2D6 phenotype and age on endoxifen steady-state concentrations and explored the clinical utility of therapeutic drug monitoring (TDM) to guide tamoxifen therapy.
View Article and Find Full Text PDFClin Pharmacol Ther
September 2025
Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Tanenbaum Centre for Pharmacogenetics, Toronto, Ontario, Canada.
Pharmacogenomics enables the personalization of drug therapy by linking genetic variations to differences in drug metabolism, efficacy, and risk of adverse reactions. Genetic polymorphisms within cytochrome P450 (CYP) genes significantly affect enzyme activity, influencing drug plasma levels, responses, and safety. Central to this process is accurate genotype-to-phenotype translation, especially for the CYP enzyme family, which metabolizes 70-80% of clinically used drugs.
View Article and Find Full Text PDFDrug Saf
September 2025
Department of PharmacoTherapy, -Epidemiology, and -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Background: Adverse event reporting systems are an important source of safety signals for drug use in pregnancy, but their usefulness in the identification of potential drug-drug interactions (DDIs) remains unclear.
Objective: Our objective was to explore the reliability of signal detection for pharmacokinetic DDIs during pregnancy in adverse event reporting systems, focusing on potential interactions between antipsychotics (APs) or antidepressants (ADs) and drugs modifying cytochrome P450 (CYP450) activity, increasing the occurrence of gestational diabetes mellitus (GDM).
Methods: Reports related to the use of drugs during pregnancy were identified in VigiBase, the World Health Organization (WHO) global database of adverse event reports.
Pharmgenomics Pers Med
August 2025
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Purpose: We aimed to determine the prevalence of interactions between PGx drugs metabolized by CYP2C9, CYP2C19, and CYP2D6 and drugs that act as inhibitors or inducers of those enzymes in the Swiss population.
Patients And Methods: We defined concomitant use of PGx drugs and inhibitors/inducers as instances where a claim of a PGx drug and a claim of an inducer or inhibitor concerning the same enzyme were made within a specified temporal window, either ± 5 days or ± 30 days. We assessed concomitant drug use between 2017 and 2021, using claims data from a Swiss insurance company (Helsana).