Effect of CYP3A Genetic Polymorphisms on the Pharmacokinetics of Atorvastatin (ECGPPA)

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.