Edoxaban Steady-State PK/PD in Adults With Nephrotic Syndrome

Inclusion criteria

• Nephrotic syndrome Group:

• Age between 18-70 years old
• Diagnosed with nephrotic syndrome: proteinuria≥3.5 g/24h or morning urine protein/creatinine ratio ≥3.0g/g), with serum albumin <30g/L present at the time of enrollment, with or without edema or hyperlipidemia
• Calculated creatinine clearance (CrCl) >50ml/min using the Cockcroft-Gault formula
• Actual body weight >60kg, and body mass index within the range of 18.5-28kg/m2
• Signed informed consent form
• Healthy volunteer Group:

• Age between 18-70 years old
• Serum albumin ≥40g/L
• Calculated CrCl >50ml/min using the Cockcroft-Gault formula
• Actual body weight >60kg, and body mass index within the range of 18.5-28kg/m2
• Signed informed consent form

Exclusion criteria

• Serun albumin <30 g/L for other reasons in patients with nephrotic syndrome as judged by the investigator
• Prolonged PT, INR, APTT at baseline (defined as greater than the upper limit of normal values)
• Platelet count <100×109/L or ≥300×109/L due to hematological diseases confirmed by laboratory tests
• History of: gastrointestinal bleeding, intracranial hemorrhage, hemoptysis, or other clinically documented bleeding from internal organs within the last 3 months; surgery (except >3 days after renal biopsy without bleeding complications) or trauma. Bleeding complications after renal biopsy are defined as: ① bleeding (hematuria, perirenal hematoma, or arteriovenous fistula) that occur after renal biopsy requiring transfusion, resulting in altered hemodynamics, or requiring surgery or interventional treatment; ② symptomatic perirenal hematoma; and ③visible hematuria that persist for >3 days postoperatively.
• A lesion or condition with a significant risk of major bleeding, such as current or recent gastrointestinal ulcer, malignant tumors with a high risk of bleeding, esophageal varices, arteriovenous malformations, vascular aneurysms, or major intravertebral or intracerebral vascular malformations.
• Serious bleeding disorders as judged by the investigator
• Systemic lupus erythematosus with or without renal damage
• Bleeding or thrombophilia disorders as judged by the investigator
• History of stroke
• History of congestive heart failure (New York grade II or above) at the time of screening
• Liver dysfunction (cirrhosis or bilirubin >2×, and serum transaminases >3×, upper limit of normal)
• Use of (but not limited to) the prescription medications that are inhibitors or inducers of CYP3A4 and/or P-gp within the past 14 days:

• CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, etc.) ②CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin, etc.)

• P-gp inducers (e.g., apalutamide, rifampicin, etc.) ④ P-gp inhibitors (e.g., dronedarone, cyclosporine, erythromycin, ketoconazole, quinidine, verapamil, amiodarone, etc.) ⑤Selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)
• Use of antiplatelet and/ or anticoagulant agents within 5 half-lives (at least 7 days): including but not limited to heparin, heparin derivatives, aspirin, clopidogrel, prasugrel, nonsteroidal anti-inflammatory drugs, warfarin, rivaroxaban, dabigatran, apixaban, etc.
• Pregnant or breastfeeding women or women of childbearing age without contraception
• Uncontrolled severe hypertension (SBP≥180mmHg, DBP≥110mmHg)
• Conditions considered unsuitable for inclusion in this study, judged by investigator
• Patients with hypersensitivity to the active ingredient or other excipients of the Edoxaban and enoxaparin sodium
• History of immune-mediated heparin-induced thrombocytopenia (HIT) or presence of circulating antibodies within the previous 100 days.
• Spinal or epidural anesthesia or local anesthesia within 24 hours prior to the administration of enoxaparin sodium and Edoxaban