Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Exclusion Criteria

• •(I)Chinese Healthy Volunteers
• •(II)Chinese Patients
• •With history of immunodeficiency disease, including positive HIV index;
• •Positive Hepatitis B surface antigen (HBsAg) and HCV index;
• •Combined therapy of CYP3A4 strong inhibitors and P-gp inhibitors (e.g., systemic pyrrole antifungal agents such as ketoconazole, itraconazole, voriconazole and posaconazole; human immunodeficiency virus (HIV) - protease inhibitors such as ritonavir), CYP3A4 strong inducers and P-gp inducers (e.g., rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's Wort, etc.) in 14 days before treatment with NOACs;
• •Severe liver dysfunction and abnormal renal function;
• •Include contraindications of NOACs, such as hypersensitivity, active bleeding, moderate or severe liver disease, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days.