Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin

Study Overview
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Brief Summary
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The aim of the study is to investigate the effects of CYP3A polymorphisms on the pharmacokinetics of Atorvastatin in Chinese subjects with coronary heart disease.

Detailed Description
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Large variability exists in the individual response to statins. CYP3A polymorphisms likely contribute to variable response to those drugs primarily metabolized by CYP3A including atorvastatin.

Official Title
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Study the Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin in Chinese Subjects With Coronary Heart Disease

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. Subjects must be >=35 years and <=70 years of age. Subjects must have an LDL-C concentration >=2.6 mmol/L and TC concentration >=4.14 mmol/L Body mass index (BMI) must be within the range of 19 to 30 for patients. Subjects must have documented coronary heart disease with one or more of the following features: Documented stable angina (with evidence of ischemia on exercise testing) History of myocardial infarction History of percutaneous coronary intervention (with or without stent placement) Documented history of unstable angina or non-Q wave myocardial infarction. Exclusion Criteria: Diabetes and endocrine or metabolic disease. Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV. Uncontrolled cardiac arrhythmia. Uncontrolled hypertension (Systolic BP >160 mm Hg and/or Diastolic BP >100 mmHg on two consecutive measurements). Liver or kidney disease confirmed by abnormal lab values or function. Smokers who report cigarette use of more then 10 cigarette per day. Subjects who consume >2 alcoholic drinks a day. (A drink is: a can of beer, glass of wine, or single measure of spirits). Known human immunodeficiency virus (HIV) positive. Cancer. Subjects who are on any of the following concomitant medications: Medications that are potent inhibitors of CYP3A, including cyclosporine, itraconazole, fluconazole, and ketoconazole, erythromycin or clarithromycin, nefazodone, protease inhibitors,mibefradil and large amounts of grapefruit juice (>1 quart/day). Lipid-lowering agent: niacin (>200 mg/day) taken within 5 weeks, fibric acid derivatives taken within 8 weeks.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CYP3A4*1/*1<br> | Drug: Atorvastatin<br>* The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.<br>* Other names: Atorvastatin Calcium Tablets;|
| Active Comparator: CYP3A4*1/*1G<br> | Drug: Atorvastatin<br>* The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.<br>* Other names: Atorvastatin Calcium Tablets;|
| Active Comparator: CYP3A4*1G/*1G<br> | Drug: Atorvastatin<br>* The subjects will receive atorvastatin (20 mg single dose) orally with approximately 240 ml of water. Blood samples(4 mL) will be taken prior to dosing and at 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24 and 48 h after drug administration.<br>* Other names: Atorvastatin Calcium Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the area under the plasma concentration versus time curve (AUC) and Area under the plasma concentration versus time curve (AUC) of atorvastatin with different CYP3A4*1G genotypes. |  | 48h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetics of atorvastatin in Chinese with coronary heart disease. |  | 48h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atorvastatin, genetic polymorphisms, coronary heart disease, pharmacokinetics, CYP3A