Explore the vast range of titles available.

AimsWhile nafamostat mesylate (NM) and sodium citrate serve as commonly used extracorporeal anticoagulants in clinical practice, the characteristics and potential risks of their adverse events (AEs) need to be systematically evaluated. This study comparatively analyzed the reporting characteristics of the AEs of the above-mentioned two drugs based on the World Health Organization Adverse Drug Reaction Reporting Database (WHO-VigiAccess), to identify their safety signals and provide evidence-based guidance for optimizing their clinical uses.MethodsMining of the global AE reporting data of NM and sodium citrate was conducted using the WHO-VigiAccess database, with the data collected until 29 December 2024. Statistical analysis was performed using the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM). The signal strengths of the AEs of the two drugs at the system organ class and preferred term levels were systematically evaluated in combination with the standardized coding MedDRA.ResultsThis study included 1,572 NM-related reports (59 AEs) and 485 sodium citrate-related reports (102 AEs). NM AEs were mainly concentrated in immune system diseases (23.80%), skin and subcutaneous tissue diseases (16.25%), and gastrointestinal diseases (10.10%), with strong disproportionality signals observed for thrombosis in devices (n = 18, ROR = 264.71), shock (n = 119, ROR = 186.27) and anaphylactoid shock (n = 4, ROR = 143.45). In contrast, sodium citrate-related AEs primarily included systemic diseases with various reactions at the administration site (15.75%) and gastrointestinal disorders (11.63%). The reporting proportion of mortality for sodium citrate (2.83%) was higher than that for NM, although this finding may be influenced by reporting bias and confounding by indication. In addition, this study detected signals not described in the instructions, such as citrate toxicity (ROR = 6,740.61) and spinal muscular atrophy (ROR = 665.94). Both drugs shared several high-incidence AEs, including pruritus, vomiting and dyspnea, but there are significant differences in gender, age and geographical distribution.ConclusionThe use of NM was associated with a strong disproportionality signal for severe immune-related AEs, such as anaphylactic shock, and requires strengthened monitoring. The metabolic complications of sodium citrate and its exposure risks during pregnancy require targeted optimization of medication strategies. Real-world data suggested that both drugs may cause AEs that were not mentioned in the instructions, so risk management needs to be improved through dynamic pharmacological vigilance. This study provided important references for individualized selection and safety management of anticoagulation regimens for patients requiring hemodialysis.

[This corrects the article DOI: 10.3389/fphar.2025.1648623.].

AimThe COVID-19 pandemic caused by infection with the novel coronavirus SARS-CoV-2 is urging the scientific community worldwide to intense efforts for identifying and developing effective drugs and pharmacologic strategies to treat the disease. Many of the drugs that are currently in (pre)clinical development are addressing late symptoms of the disease. This review focuses on potential pharmacologic intervention at an early stage of infection which could result in less-infected individuals and less cases with severe COVID-19 disease due to reduced virus entry into the cells.MethodWe scanned the literature for evidence on drugs that target the virus entry machinery into host cells and consist mainly of ACE2 and TMPRSS2, as well as other cellular molecules regulating ACE2 expression, such as ADAM-17 and calmodulin.ResultsSeveral drugs/drug classes have been identified. Most of them are already used clinically for other indications. They include recombinant soluble ACE2, indirect ACE2 modulators (angiotensin receptor blockers, calmodulin antagonists, selective oestrogen receptor modifiers), TMPRSS2 inhibitors (camostat mesylate, nafamostat mesylate, antiandrogens, inhaled corticosteroids) and ADAM-17 enhancers (5-fluorouracil).ConclusionSeveral agents have potential for prophylactic and therapeutic intervention at the early stages of SARS-CoV-2 infection and COVID-19 disease and they should be urgently investigated further in appropriate preclinical models and clinical studies.

This is a series of reports describing how increasing the time interval between the administration of nafamostat mesylate (NM) and levocarnitine can suppress adverse reactions in maintenance hemodialysis patients after medication. Clinical assessments and medical record collection were conducted by nephrologists and nurses, while laboratory tests were performed by specialist doctors. Increasing the time interval between NM and levocarnitine administration (15–25 minutes) reduced adverse drug reactions, including nausea and vomiting, in 4 patients. This may provide clinical doctors with new insights and research directions when using levocarnitine and NM for dialysis treatment.

Background Nafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action. Methods Time to first dose of nafamostat administration was tested on rats after contusive SCI. The optimal time window of nafamostat was screened by evaluating hindlimb locomotion and electrophysiology. As nafamostat is a serine protease inhibitor known to target thrombin, we used argatroban (Arg), a thrombin-specific inhibitor, as a positive control in the time window experiments. Western blot and immunofluorescence of thrombin expression level and its enzymatic activity were assayed at different time points, as well its receptor, the protease activated receptor 1 (PAR1) and downstream protein matrix metalloproteinase-9 (MMP9). Blood–spinal cord barrier (BSCB) permeability leakage indicator Evans Blue and fibrinogen were analyzed along these time points. The infiltration of peripheral inflammatory cell was observed by immunofluorescence. Results The optimal administration time window of nafamostat was 2–12 h post-injury. Argatroban, the thrombin-specific inhibitor, had a similar pattern. Thrombin expression peaked at 12 h and returned to normal level at 7 days post-SCI. PAR1, the thrombin receptor, and MMP9 were significantly upregulated after SCI. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). Nafamostat and argatroban significantly downregulated thrombin and MMP9 expression as well as thrombin activity in the spinal cord. Nafamostat inhibited thrombin enrichment in endothelial cells. Nafamostat administration at 2–12 h after SCI inhibited the leakage of Evans Blue in the epicenter and upregulated tight junction proteins (TJPs) expression. Nafamostat administration 8 h post-SCI effectively inhibited the infiltration of peripheral macrophages and neutrophils to the injury site. Conclusions Our study provides preclinical information of nafamostat about the administration time window of 2–12 h post-injury in contusive SCI. We revealed that nafamostat functions through inhibiting the thrombin-mediated BSCB breakdown and subsequent peripheral immune cells infiltration.

Purpose The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. Patients and methods Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients’ baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. Results In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. Conclusion Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

For hemodialysis patients at high risk of bleeding, a regional anticoagulant can be used, such as citrate or nafamostat mesylate (NM). The objective of this study was to evaluate NM as an alternative to citrate for anticoagulation in hemodialysis patients at high risk of bleeding. This retrospective single-center study included consecutive patients in our dialysis center treated with either citrate or NM anticoagulation for hemodialysis from January 2022 to December 2023.The primary outcome was major clotting, defined as premature dialysis due to extracorporeal circuit clotting. The secondary outcome was the incidence of a major bleeding episode during or after hemodialysis. In total, 651hemodialysis sessions were performed in 196 patients and were compared (289 citrate and 362 NM anticoagulation). A lower number of premature dialysis due to clotting occurred in the NM sessions compared to citrate sessions (0.84% vs.5.19%,  = 0.001). NM was associated with a lower risk of major clotting compared with citrate during treatment (OR:0.063; CI: 0.008-0.475;  = 0.007). Regarding second outcome, no more major bleeding events related to NM occurred compared to citrate. Among hemodialysis patients with high risk of bleeding, anticoagulation with NM, compared with citrate anticoagulation, provided relatively better efficacy, with no bleeding increment. NM is a valid alternative to citrate for hemodialysis patients at high risk of bleeding.

To explore the application of nafamostat mesylate in the extracorporeal carbon dioxide removal combined with continuous renal replacement therapy. We analyzed the cases of 5 patients who underwent extracorporeal carbon dioxide removal combined with continuous renal replacement therapy due to severe hypercapnia with acute kidney injury at the Blood Purification Center of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2023 to October 2024. The treatments were performed using the OMNI blood purification system (B. Braun Avitum AG, Melsungen, Germany), equipped with a PMP polymethylpentene membrane lung (1.81 m , Eurosets Medolla, Italy), with unhumidified pure oxygen connected to the ECCO R membrane lung via an oxygen supply device at a rate of 6-7 L/min, and in series with the blood filter (OMNIFilter 16, polyethersulfone membrane, 1.6 m ). CRRT was performed using the CVVH mode, with sodium lactate replacement fluid at a flow rate of 2-3 L/h. A 14Fr dual-lumen dialysis catheter (ARROW) was placed under ultrasound-guided puncture in the femoral vein. The extracorporeal blood flow was maintained between 300 and 400 mL/min. Continuous infusion of NM (50-30 mg/h) was used to maintain anticoagulation. Demographic and physiological data were collected (including vital signs, ventilation parameters, blood gas, electrolytes, DIC, etc.), with blood sampling points before and after the filter as well as peripheral blood. Among the 5 patients, there were 2 males and 3 females, with an average age of 83.2 ± 9.6 years old. A total of 22 treatments were administered, with an average treatment time of 8.8 ± 1.6 h. All patients had primary diseases of severe pneumonia and chronic obstructive pulmonary disease; among them, 4 had combined renal injury, and 3 patients were on mechanical ventilation. During the total of 22 treatments, there was 1 instance of dialyzing tube occlusion which led to the end of treatment 2 h early, while the other 21 treatments were completed smoothly, with no occlusion occurring in the filter, ECCO R membrane lung, or dialyzing tube. No adverse events such as bleeding occurred in the patients, and there were no statistically significant differences in APTT and PT after treatment compared to before. During the treatment, statistically significant improvements in PaCO and blood pH were observed. Blood pressure, heart rate, and blood oxygen saturation remained stable. Extracorporeal carbon dioxide removal combined with continuous renal replacement therapy can partially replace lung ventilation function and improve hypercapnia. NM can be used as an anticoagulant in this technology, with an ideal anticoagulation effect and no significant risk of bleeding.

Keywords: COVID-19, Adverse events, Nafamostat mesylate, Favipiravir

To better understand nafamostat mesylate (NM) dose requirements during extracorporeal membrane oxygenation (ECMO), this study investigated its pharmacokinetic/pharmacodynamic (PK/PD) properties by comparing samples from the systemic circulation of patients and from the ECMO circuit. It specifically examined the relationship between NM concentration and activated partial thromboplastin time (aPTT) changes, aiming to provide a foundation for future dosing optimization. In this prospective study, 24 ECMO patients received a continuous infusion of NM through a dedicated stopcock located before the ECMO pump. This placement targets the anticoagulant effects of NM specifically to the ECMO circuit without substantially affecting the patient's overall coagulation status. The starting dose was 15 mg/h, adjusted to keep the aPTT within a target range of 40-80 s. Blood samples were collected from both the patient's central venous catheter and the ECMO circuit for PK/PD analysis using a nonlinear mixed effects model. The PK profiles of NM, derived from samples taken from both the patient's catheter and the ECMO circuit, were best described by a two-compartment model. In the PK/PD models, the effect of NM on prolonging aPTT was described using a turnover model. NM was shown to inhibit the decrease in aPTT in the turnover model. In the patient model, the maximum inhibitory effect (Imax) of NM on the reduction of aPTT was 35.5%, and the concentration of NM required to achieve half of this maximum effect (IC50) was 350 μg/L. On the other hand, in the ECMO model, the Imax for aPTT reduction was 43.6%, with an IC50 of 581 μg/L. The PK/PD models developed from samples collected from both the patient and the ECMO circuit indicate significant differences in PD. Given the observed variability and the high risk of bleeding in ECMO patients, a predictive model incorporating these differences and patient-specific variables could significantly improve anticoagulation management.