CYP2D6 Polymorphism Defining UM, IM, NM and PM Status in Unselected Medically Treated Patients of General Practice in Austria
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 289
- 试验地点
- 1
- 主要终点
- Frequency of Metabolizer Status (PM, IM, NM, UM) in Patients
研究概览
简要总结
The CYP 2D6 enzyme metabolizes a significant number of drugs frequently prescribed in general practice/ family medicine. Various genetically different variants define if the patient is an ultra-rapid (UM), an normal (NM) (the normal case), an intermediate (IM) or a poor metabolizer (PM). It is estimated that approximately 20- 25 % of frequently described drugs are activated to more active or metabolized to ineffective or less effective drugs by CYP 2D6. Substrates of CYP 2D6 are mainly antidepressants, neuroleptics, opioids (e.g. codeine), beta-blockers, anti-arrhythmic drugs and various other single drugs. In case of an UM a drug can be metabolized too rapidly losing its therapeutic effect, requiring a higher dosage, or it can have a toxic effect, if it is converted too rapidly in the effective form (e.g. codeine). If metabolized too slowly (PM) it can accumulate and reach toxic levels.
In this observational study (1) data relating to the number of patients of a single Austrian general practice receiving one or more drugs metabolized by CYP 2D6 are collected by extracting their electronic records of the last 3 years. In addition (2) consecutive patients with unknown genetic status of their CYP 2D6 enzyme visiting the surgery for a routine blood test due to various reasons, are additionally tested for their CYP 2D6 metabolizing status, if they actually take a drug metabolized by CYP 2D6.
The aim of the study is to generate CYP 2D6 polymorphism data from Caucasian patients of an average Austrian general practice for the first time, which allows to group patients according to their NM, UM, IM and PM status. This can be of considerable clinical relevance when prescribing specific drugs. This study tries to investigate in how many patients the knowledge of the CYP 2D6 metabolizing status could have an influence on choosing the actually prescribed drug. In addition we plan to describe the distribution of frequent and relevant CYP 2D6 alleles including their combinations in patients of an average Austrian general practice for comparison reasons with other Caucasian populations.
详细描述
Study population:
Unselected consecutive patients of the practice office visiting the surgery for a routine blood sampling due to various medical conditions and who are prescribed or have been prescribed drugs metabolized by the CYP2D6 enzyme (or drugs being a strong inhibitor of CYP 2D6) during the last 3 years. Only in these patients CYP2D6 polymorphism is determined using a fraction of the EDTA-blood sample. No further genetic investigations or additional blood collections are performed.
Patients who are considered to be eligible to participate in the study have to sign an informed consent after being informed about the aims of the study.
Blood sampling and processing of the specimens:
A standardized blood sampling using a Vacutainer system with filling of an EDTA tube (4 ml) for the red and white blood count is performed. 300 microliters of the collected blood are used for further determination of the CYP2D6 polymorphism.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with clinical diagnosis of hypertension, diabetes, chronic heart failure, hyperlipidemias, depression, schizophrenia, cardial arrhythmias, thyroid diseases and dementia
排除标准
- •acute infectious diseases
结局指标
主要结局
Frequency of Metabolizer Status (PM, IM, NM, UM) in Patients
时间窗: 1 Year
Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived. A patient can be considered a ultra-rapid (UM), a normal (NM), an intermediate (IM), or a poor metabolizer (PM) of a given drug
Frequency of CYP2D6 Alleles in Patients
时间窗: 1 Year
The frequency of 19 different CYP2D6 alleles in 287 patients is determined. In 2 out of all 289 patients the determination was not possible due to technical problems. Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived.
Frequency of CYP2D6 Genotypes in Patients
时间窗: 1 Year
The frequency of 61 different CYP2D6 genotypes in 287 patients is determined. In 2 out of all 289 patients the determination was not possible due to technical problems. Remark: each participant possesses a) two individual CYP2D6 alleles, b) from the combination of these two alleles one individual genotype is derived and c) from this genotype the genetically determined metabolizer status (PM, IM, NM, UM) is derived.
次要结局
- Number of Participants in Whom the Family Physician Considered Prior Knowledge of Their Metabolizer Status Important Before the CYP2D6-specific Drug Was Prescriped.(1 Year)
- Specific Number of Patients of the Whole Practice Population Whose Electronic Health Records (EHRs) Were Assessed.(1 Year)
研究者
Gustav Kamenski
General Practitioner/Family Physician
Karl Landsteiner Institute for Systematics in General Medicine