The aim of this study is to investigate the effects of oral D-mannose tablets for 2 consecutive weeks on the pharmacokinetics of dabigatrun etexilate, a P-glycoprotein probe substrate drug, in healthy adults

This study is a prospective, sinale-center, open-label clinical studly, with adult healthy subiects as the research subjects. Healthy adult subjects will receive a single oral dose of 110mg (low dose specification in the instructions) or lower of dabigatran etexilate on day 1 and day 16 of the trial period. Blood samples for dabigatran plasma concentration determination at 0 h(before dosing)2 h, 4 h, 6 h, 12 h and 24 h after dosing will be taken. Subjects will take 3g (1g*3 tablets) of D-mannose tablets every morning and evening from the 2nd day to the 15th day of the trial period, with a total of 6g/day (medium dose specification in the instructions). Blood samples for detection of glycotomic serum concentrations such as D-mannose will be taken 0h before oral administration of dabigatran etexilate on day 1 and 1.5h after oral administration of D-mannose each morning on days 2, 8, and 15 of the trial period.

Inclusion Criteria:

1. With full capacity for civil conduct, the age of healthy male subjects is ≥18 years old and ≤45 years old
2. Male weight ≥50 kg; body mass index (BMI) within the range of 19.0~27.0 (including upper and lower limits)
3. Creatinine clearance rate (CRCL: calculated by Cock croft-Gault equation, adult healthy subjects should have CRCL≥90mL/min

Exclusion Criteria:

1. History of fainting of needles and blood.
2. Diseases affecting intestinal P-glycoprotein: severe diarrhea (excretion more than 3 times 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. Diabetes mellitus; Impaired fasting glucose (IFG); Impaired glucose tolerance (IGT); Oral hypoglycemic agents (including the use of hypoglycemic agents for weight loss purposes).
4. Diseases or conditions with significant risk of major bleeding, such as current or recent peptic ulcer, malignant neoplasms with high bleeding risk, recent brain or spinal cord injury, recent brain, spinal cord, or eye surgery, recent intracranial hemorrhage, known or suspected Esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracranial vascular abnormalities.
5. Clinically significant active bleeding.
6. Taking anticoagulants such as unfractionated heparin (UFH), low molecular weight heparin (LMWH) and heparin derivatives (fondaparinux sodium), vitamin K antagonists, rivaroxaban or other direct thrombin inhibitors (recombinant hirudin, bivalirudin); thrombolytic drugs, or current use of antiplatelet aggregation drugs such as GPⅡb/Ⅲa receptor antagonists, ticlopidine, prasugrel, dextran, sulfinpyrazone, aspirin, etc.
7. Use of drugs that may affect the activity of intestinal p-glycoprotein within 1 week before the trial: (1) potent p-glycoprotein inhibitors: amiodarone, verapamil, diltiazem, quinidine, dronedarone, tacrolimus, cyclosporine, protease inhibitors(indinavir, nelfinavir, saquinavir, lopinavir), macrolide antibiotics (erythromycin, clarithromycin, telithromycin, chloramphenicol), azole antifungal drugs (ketoconazole, itraconazole, Posaconazole, voriconazole, fluconazole, miconazole), nefazodone, cobicistat, cimetidine, ciprofloxacin, cyclosporin, fluvoxamine, imatinib, St. John's Wort, ranolazine; (2) Potent P-glycoprotein inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, antiandrogens(enzalutamide, apalutamide), phenobarbital, dexamethasone.
8. Those who have a history of smoking and drinking in the past and who do not agree with the prohibition of smoking and drinking during the trial period: smokers (the average daily cigarettes smoked more than 5 cigarettes within one month before the test); alcoholism: (the average daily drinking within one month before the test≥100mL high-quality liquor/200mL wine / 600mL beer).
9. History of gastrointestinal surgery such as gallbladder or appendectomy, bariatric surgery, etc. within the past 5 years.
10. Positive virological test (human immunodeficiency virus antibody (HIV-Ab), syphilis serological test, hepatitis B virus surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab)) within 6 months before screening.
11. Those who have participated in clinical trials of any dug or medial device within 6 months before screening (in the case of drug clinical trials those who participated in the previous clinical trial before screening have more than 5 half-lives).
12. Subjects who are considered by the investigator to have any factors that are not suitable for participating in this trial.