Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.
Adult ; Child ; Humans ; Adrenergic Uptake Inhibitors/therapeutic use* ; Atomoxetine Hydrochloride/therapeutic use* ; Attention Deficit Disorder with Hyperactivity/genetics* ; Cytochrome P-450 CYP2D6/therapeutic use* ; Drug Monitoring ; Genetic Testing ; Propylamines/therapeutic use* ; Treatment Outcome

The aim of the study was to evaluate the association between genetic polymorphisms of CYP2D6 and outcomes in breast cancer patients with tamoxifen treatment. We evaluated the CYP2D6 genetic polymorphisms in 766 breast cancer patients. Among them, 110 patients whose samples were prospectively collected before surgery and treated with tamoxifen were included to evaluate the association between CYP2D6 and outcomes. The genotypes of CYP2D6 were categorized as extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) according to the activity score. The clinicopathologic features of 110 patients were not significantly different among the three groups except for the T-stage and nodal status. The high T-stage and axillary metastasis were more frequent in the PM group. While recurrence-free and overall survival in the PM group was poorer than the other groups, there was no significant difference between the EM and the IM group. The difference between the PM and the other groups on univariate analysis disappeared on multivariate analysis. These conflicting results suggest that the clinical value of CYP2D6 polymorphisms is still unclear and more large-sized and comprehensively designed trials are necessary.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Hormonal/*therapeutic use ; Breast Neoplasms/drug therapy/*genetics/mortality ; Cytochrome P-450 CYP2D6/*genetics ; Female ; Genotype ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Staging ; *Polymorphism, Single Nucleotide ; Tamoxifen/*therapeutic use

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.
Adult ; Chromatography, High Pressure Liquid ; Clomiphene/blood/metabolism/*therapeutic use ; Cytochrome P-450 CYP2D6/*genetics ; Estrogen Antagonists/analysis/metabolism/therapeutic use ; Female ; Genotype ; Humans ; Infertility/*drug therapy/genetics ; Ovulation Induction ; Phenotype ; *Polymorphism, Genetic ; Republic of Korea ; Tandem Mass Spectrometry

The objective of this study was to investigate the correlation between the gene polymorphisms of drug metabolizing enzymes and the outcome of the first induction chemotherapy in patients with de novo acute myeloid leukemia (AML). 113 de novo AML patients were enrolled in this study. The genotypes of 11 single nucleotide polymorphisms (SNP) in drug metabolizing enzymes were detected by the SNPstream(®) Genotyping System. The correlation between the distribution of genotypes and the complete remission rate of first induction chemotherapy was analyzed by logical regression. The results showed that patients with variant genotype of CYP2D6 (rs16947) had a lower complete remission (CR) rate, as compared to those with wild type (p = 0.033, OR = 0.32, 95%CI 0.112 - 0.915); meanwhile the patients with variant genotype of GSTO2 (rs156697) had a higher CR rate as compared to those with wild type (p = 0.011, OR = 3.023, 95%CI 1.289 - 7.089). Combined analysis of the above polymorphisms, showed that patients with variant genotype of CYP2D6 and wild genotype of GSTO2 (V + W) had lower CR rates in comparison to patients with wild genotypes of both polymorphisms (p = 0.017, OR = 0.183, 95%CI 0.045 - 0.735). It is concluded that CYP2D6 (rs16947) and GSTO2 (rs156697) polymorphisms are independent factors influencing CR rates of the first induction chemotherapy in de novo AML patients.
Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Child ; Cytochrome P-450 CYP2D6 ; genetics ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Remission Induction ; Treatment Outcome ; Young Adult

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.
Anticoagulants/therapeutic use ; Antidepressive Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Antitubercular Agents/therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Coronary Artery Disease/drug therapy/genetics ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2D6/genetics ; Depressive Disorder/drug therapy/genetics ; Genotype ; Isoniazid/therapeutic use ; Laboratories, Hospital/standards ; Methyltransferases/genetics ; Pharmacogenomic Testing/*methods/standards ; Platelet Aggregation Inhibitors/therapeutic use ; Pulmonary Embolism/drug therapy/genetics ; Ticlopidine/analogs & derivatives/therapeutic use ; Tuberculosis/drug therapy/genetics ; Vitamin K Epoxide Reductases/genetics ; Warfarin/therapeutic use