BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fi...BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.展开更多
Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acut...Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.展开更多
BACKGROUND Nafamostat mesylate(NM)may prove to be one of the key drugs effective against coronavirus disease 2019(COVID-19)because of its anti-viral properties and the potential to manage coagulopathy.However,NM tends...BACKGROUND Nafamostat mesylate(NM)may prove to be one of the key drugs effective against coronavirus disease 2019(COVID-19)because of its anti-viral properties and the potential to manage coagulopathy.However,NM tends to increase serum potassium levels.CASE SUMMARY We observed hyperkalemia immediately after NM administration(200 mg/d)in four consecutive patients who were admitted to the Kanazawa University Hospital with severe COVID-19 pneumonia.Urinary potassium excretion decreased after NM administration in three patients who underwent urinalysis.CONCLUSION NM is likely to produce hyperkalemia in patients with COVID-19.Therefore,it is necessary to monitor serum potassium values closely after NM initiation in COVID-19 patients who need respiratory support.展开更多
Continuous renal replacement therapy (CRRT) is the preferred dialysis modality in critical care settings for patients with hemodynamic instability. Nafamostat mesylate (NM) is an anticoagulant commonly used (mainly in...Continuous renal replacement therapy (CRRT) is the preferred dialysis modality in critical care settings for patients with hemodynamic instability. Nafamostat mesylate (NM) is an anticoagulant commonly used (mainly in Japan) during CRRT in patients with high bleeding risk. In this study, we evaluated the pharmacokinetics of NM during CRRT. Patients undergoing CRRT therapy and using NM as the anticoagulant in the intensive care unit were enrolled in the study. Blood was collected from the CRRT circuit just after blood removal, just before and after the membrane for CRRT, and from the filtrates after the membrane. NM concentrations were measured using high-performance liquid chromatography. NM was detected in the intracorporeal circulation during CRRT in some cases, and liver enzymes were severely elevated in almost all of the cases. Coagulation time was prolonged even before the initiation of NM administration in these cases and may be associated with liver damage. This study suggests that NM dosage should take into account liver damage assessed by elevated liver enzymes.展开更多
Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute pancreatitis.The impurities in nafamostat mesylate,the active pharmaceutical ingredient(API),were profiled via high performance liquid ...Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute pancreatitis.The impurities in nafamostat mesylate,the active pharmaceutical ingredient(API),were profiled via high performance liquid chromatography tandem ion trap coupled with time-of-flight mass spectrometer(HPLC-IT-TOF/MS).The chromatography was performed on an ACE-3 C18 column(200 mm4.6 mm,3 mm)using methanol and 0.1%formic acid in purified water as mobile phase at a flow rate of 1.0 mL/min.The ions were detected by IT-TOF/MS with a full-scan mass analysis from m/z 100 to 800.In total,eleven impurities were detected in nafamostat mesylate API.The impurity profile was estimated based on the HPLC-IT-TOF/MS data,including accurate masses,MSn fingerprints of fragmentation pathways and a series of double-charged ions.Finally,seven impurities were identified and reported for the first time.The results will provide technical support for the quality control and clinical safety of nafamostat mesylate.展开更多
Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection.It is the primary cause of death in the intensive care unit,posing a substantial challenge to human health and medical res...Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection.It is the primary cause of death in the intensive care unit,posing a substantial challenge to human health and medical resource allocation.The pathogenesis and pathophysiology of sepsis are complex.During its onset,pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions,possibly leading to hyperinflammation,immuno-suppression,and long-term immune disease.Of all critical outcomes,hyperinflammation is the main cause of early death among patients with sepsis.Therefore,early suppression of hyperinflammation may improve the progno-sis of these patients.Nafamostat mesilate is a serine protease inhibitor,which can inhibit the activation of the complement system,coagulation system,and contact system.In this review,we discuss the pathophysiological changes occurring in these systems during sepsis,and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.展开更多
文摘BACKGROUND Recent studies on dialysis anticoagulation therapy in patients with renal failure have shown that Nafamostat mesylate,a broad-spectrum potent serine protease inhibitor,has strong anticoagulation and anti-fiber activity.AIM To evaluate the efficacy and safety of Nafamostat mesylate in patients with end-stage renal failure.METHODS Seventy-five patients with end-stage renal failure who received hemodialysis at our hospital between January 2020 and August 2021 were selected and divided into the observation group(Nafamostat mesylate for injection,n=33)and control group(heparin sodium injection,n=32).General patient data,indicators of clinical efficacy,dialyzer hemocoagulation parameters,coagulation function indices,and hemoglobin concentration and platelet count before and after treatment,and the occurrence of adverse reactions after treatment were compared between the two groups.RESULTS The two groups showed no significant differences in general patient data(P>0.05).The post-treatment effectiveness rate in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the number of patients in grade I(P>0.05),while the number of patients in grade 0 was lower in the control group,and the number of patients in grades II and III was higher in the control group(P<0.05).The post-treatment prothrombin time,activated partial thromboplastin time,thrombin time,and international normalized ratio values in the control group were higher than those in the observation group,while the fibrinogen level in the control group was lower than that in the observation group(P<0.05).The two groups showed no significant difference in the platelet count and hemoglobin level before and after treatment(P>0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(P<0.05).CONCLUSION Treatment of patients showing end-stage renal failure with Nafamostat mesylate can significantly improve therapeutic efficacy and has high safety and clinical value.
文摘Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.
文摘BACKGROUND Nafamostat mesylate(NM)may prove to be one of the key drugs effective against coronavirus disease 2019(COVID-19)because of its anti-viral properties and the potential to manage coagulopathy.However,NM tends to increase serum potassium levels.CASE SUMMARY We observed hyperkalemia immediately after NM administration(200 mg/d)in four consecutive patients who were admitted to the Kanazawa University Hospital with severe COVID-19 pneumonia.Urinary potassium excretion decreased after NM administration in three patients who underwent urinalysis.CONCLUSION NM is likely to produce hyperkalemia in patients with COVID-19.Therefore,it is necessary to monitor serum potassium values closely after NM initiation in COVID-19 patients who need respiratory support.
文摘Continuous renal replacement therapy (CRRT) is the preferred dialysis modality in critical care settings for patients with hemodynamic instability. Nafamostat mesylate (NM) is an anticoagulant commonly used (mainly in Japan) during CRRT in patients with high bleeding risk. In this study, we evaluated the pharmacokinetics of NM during CRRT. Patients undergoing CRRT therapy and using NM as the anticoagulant in the intensive care unit were enrolled in the study. Blood was collected from the CRRT circuit just after blood removal, just before and after the membrane for CRRT, and from the filtrates after the membrane. NM concentrations were measured using high-performance liquid chromatography. NM was detected in the intracorporeal circulation during CRRT in some cases, and liver enzymes were severely elevated in almost all of the cases. Coagulation time was prolonged even before the initiation of NM administration in these cases and may be associated with liver damage. This study suggests that NM dosage should take into account liver damage assessed by elevated liver enzymes.
基金This work was financially supported by the National Major Science and Technology Projects of China(2017ZX09101001)the Double First-Class University Project(CPU2018GY33).
文摘Nafamostat mesylate is a serine protease inhibitor used in the treatment of acute pancreatitis.The impurities in nafamostat mesylate,the active pharmaceutical ingredient(API),were profiled via high performance liquid chromatography tandem ion trap coupled with time-of-flight mass spectrometer(HPLC-IT-TOF/MS).The chromatography was performed on an ACE-3 C18 column(200 mm4.6 mm,3 mm)using methanol and 0.1%formic acid in purified water as mobile phase at a flow rate of 1.0 mL/min.The ions were detected by IT-TOF/MS with a full-scan mass analysis from m/z 100 to 800.In total,eleven impurities were detected in nafamostat mesylate API.The impurity profile was estimated based on the HPLC-IT-TOF/MS data,including accurate masses,MSn fingerprints of fragmentation pathways and a series of double-charged ions.Finally,seven impurities were identified and reported for the first time.The results will provide technical support for the quality control and clinical safety of nafamostat mesylate.
基金supported by the National Natural Science Foundation of China(grant numbers 82102287)Key dis-cipline of Shanghai’s Three-year Action Plan to Strengthen the construction of public health system(2023-2025)(grant num-bers GWVI-11.1-14).
文摘Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection.It is the primary cause of death in the intensive care unit,posing a substantial challenge to human health and medical resource allocation.The pathogenesis and pathophysiology of sepsis are complex.During its onset,pro-inflammatory and anti-inflammatory mechanisms engage in intricate interactions,possibly leading to hyperinflammation,immuno-suppression,and long-term immune disease.Of all critical outcomes,hyperinflammation is the main cause of early death among patients with sepsis.Therefore,early suppression of hyperinflammation may improve the progno-sis of these patients.Nafamostat mesilate is a serine protease inhibitor,which can inhibit the activation of the complement system,coagulation system,and contact system.In this review,we discuss the pathophysiological changes occurring in these systems during sepsis,and describe the possible targets of the serine protease inhibitor nafamostat mesilate in the treatment of this condition.
