Pharmacokinetic Study to Evaluate Dabigatran Etexilate in Elderly Subjects

Inclusion Criteria:

1. With full capacity for civil conduct, the age of adult healthy subjects is ≥18 yearsold and ≤30 years old; elderly healthy subjects ≥ 75 years old; elderly patients withatrial fibrillation are ≥75 years old.
2. Male weight ≥ 50 kg, female weight ≥ 45 kg; body mass index (BMI) within the range of 19.0~27.0 (including upper and lower limits), body mass index (BMI) = weight (kg) /height 2 (m2).
3. Creatinine clearance rate (CRCL): calculated by Cock Croft-Gault equation, adulthealthy subjects should have CRCL≥90mL/min; elderly healthy subjects should haveCRCL≥60mL/min; elderly patients with atrial fibrillation should have CRCL≥30mL/min.
4. Elderly patients with atrial fibrillation should have meet the diagnostic criteria fornon-valvular atrial fibrillation.
5. Elderly patients with atrial fibrillation are taking Dabigatran etexilate for routinetreatment.

Exclusion Criteria:

1. History of fainting of needles and blood.
2. Diseases affecting intestinal P-glycoprotein: severe diarrhea (excretion more than 3times a day with watery stool characteristics), Crohn's disease, ulcerative colitis,irritable bowel syndrome, diverticulitis, difficult Identify Clostridium infection (recurrent) or Helicobacter pylori infection.
3. Diseases affecting the activity of CYP3A in the liver: acute kidney injury, livercirrhosis, liver abscess, liver cancer, intrahepatic bile duct stones, etc.
4. Diseases affecting changes in intestinal flora: non-alcoholic fatty liver disease,diabetes, chronic constipation.
5. History of major diseases or newly discovered diseases: prostate cancer, leukemia,liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases.
6. Diseases or conditions with significant risk of major bleeding, such as current orrecent peptic ulcer, malignant neoplasms with high bleeding risk, recent brain orspinal cord injury, recent brain, spinal cord, or eye surgery, recent intracranialhemorrhage, known or suspected Esophageal varices, arteriovenous malformations,vascular aneurysms, or major intraspinal or intracranial vascular abnormalities.
7. Clinically significant active bleeding.
8. Are using anticoagulant drugs such as unfractionated heparin (UFH), low molecularweight heparin (LMWH) and heparin derivatives (fondaparinux sodium), vitamin Kantagonists, rivaroxaban or other direct thrombin Inhibitors (recombinant hirudin,bivalirudin); thrombolytic drugs; or current use of antiplatelet aggregation drugssuch as GPIIb/IIIa receptor antagonists, ticlopidine, prasugrel, dextran,sulfinpyrazone, aspirin, etc.
9. Use of drugs that may affect the intestinal flora within 1 week before the trial:Continuous use of antibiotics, Bifidobacterium triple viable bacteria powder,lactobacillus tablets, compound Lactobacillus acidophilus tablets, Bacillus subtilisdual viable bacteria enteric-coated capsules, containing bismuth subsalicylate, etc.
10. Use of drugs that may affect the activity of intestinal P-glycoprotein/CYP3A within 1week before the trial: ① Potent P-glycoprotein/CYP3A inhibitors: amiodarone,verapamil, diltiazem, quinidine, dronedarone, tacrolimus, cyclosporine, proteaseinhibitors indinavir, nelfinavir, saquinavir, lopinavir), macrolide antibiotics (erythromycin, clarithromycin, telithromycin), chloramphenicol, azole Antifungal drugs (ketoconazole, itraconazole, Posaconazole, voriconazole, fluconazole, miconazole),nefazodone, cobicistat, cimetidine, ciprofloxacin, Imatinib, St. John's Wort,Ranolazine; ② Potent P-glycoprotein/CYP3A inducers: rifampicin, carbamazepine,phenytoin, phenobarbital, dexamethasone, antiandrogens (enzalutamide, apalutamide).
11. Those who have a history of smoking and drinking in the past, and who do not agreewith the prohibition of smoking and drinking during the trial period: smokers (theaverage daily cigarettes smoked more than 5 cigarettes within one month before thetest); alcoholism (the average daily drinking within one month before the test) ≥100mLhigh-quality liquor (ethanol content ≥40%)).
12. History of gastrointestinal surgery such as gallbladder or appendectomy, bariatricsurgery, etc. within the past 6 months.
13. Positive virological test (human immunodeficiency virus antibody (HIV-Ab), syphilisserological test, hepatitis B virus surface antigen (HBsAg) or hepatitis C virusantibody (HCV-Ab)) within 3 months before screening.
14. Those who have participated in clinical trials of any drug or medical device within 1month before screening (in the case of drug clinical trials, those who participated inthe previous clinical trial before screening have more than 5 half-lives).
15. Subjects who are considered by the investigator to have any factors that are notsuitable for participating in this trial. Adult healthy subjects, with the following additional exclusion criteria:
16. Pregnant and lactating women.
17. Suffering from atrial fibrillation, hypertension, heart failure, coronary heartdisease, heart valve disease and other diseases.