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Efficacy and safety of nafamostat mesylate in patients with endstage renal failure

World Journal of Clinical Cases 2024年第1期12卷 68-75页

作者： Kun Liu Zhen-Hua Li Department of Critical Care Medicine The Third People's Hospital Of Hubei ProvinceWuhan 430030Hubei ProvinceChina Department of Critical Care Medicine General Hospital of The Yangtze River ShippingWuhan Brain HospitalWuhan 430015Hubei ProvinceChina

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(P0.05),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(P0.05).The total number of post-treatment adverse reactions in the observation group was lower than that in the control group(Pnafamostat mesylate can significantly improve therapeutic efficacy and ha

关键词： End-stage renal failure nafamostat mesylate Effectiveness Safety study Chronic kidney diseases

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nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia

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Neural Regeneration Research 2020年第12期15卷 2217-2234页

作者： George Zaki Ghali Michael George Zaki Ghali United States Environmental Protection Agency ArlingtonVAUSA Department of Toxicology Purdue UniversityWest LafayetteINUSA Department of Neurological Surgery University of California San FranciscoSan FranciscoCAUSA Department of Neurobiology and Anatomy Drexel University College of MedicinePhiladelphiaPAUSA

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.

关键词： apoptosis cerebrovascular excitotoxicity infarction ischemia nafamostat mesylate necrosis neuroprotection serine protesae subarachnoid hemorrhage

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Identification of impurities in nafamostat mesylate using HPLC-ITTOF/MS:A series of double-charged ions

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Journal of Pharmaceutical Analysis 2020年第4期10卷 346-350页

作者： Yuxin Zhang Lufan An Lin Zhang Rulin Wang Yuan Tian Zunjian Zhang Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical SchoolNanjing210008PR China Jiangsu D&R Pharmaceutical Corporation Taizhou225312PR China Department of Pharmacy General Hospital Tianjin Medical UniversityTianjin300052PR China Key Laboratory of Drug Quality Control and Pharmacovigilance(Ministry of Education) China Pharmaceutical UniversityNanjing210009PR China

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.

关键词： nafamostat mesylate Impurity Structure identification Double-charged ion

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Evaluation of the Pharmacokinetics of nafamostat mesylate during Continuous Renal Replacement Therapy

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Open Journal of Emergency Medicine 2022年第4期10卷 157-167页

作者： Koji Konishi Satoki Inoue Masahiko Kawaguchi Department of Clinical Engineering Nara Medical University Hospital Nara Japan Department of Anesthesiology Fukushima Medical University Hospital Fukushima Japan Department of Anesthesiology Nara Medical University Hospital Nara Japan

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.

关键词： nafamostat mesylate Continuous Renal Replacement Therapy Liver Dysfunction

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A Novel Cleavage Pattern of Complement C5 Induced by Chlamydia Trachomatis Infection via the Chlamydial Protease CPAF

A Novel Cleavage Pattern of Complement C5 Induced by Chlamyd...

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第十四届全国免疫学学术大会

作者： Liang Peng Jingping Gao Zihao Hu Hongbo Zhang Lingli Tang Fuyan Wang Lei Cui Shanshan Liu Yujie Zhao Hong Xu Xin Su Xiaojing Feng Yiyuan Fang Jianlin Chen Reproductive Medicine Center Department of Obstetrics and Gynecologythe Second Xiangya HospitalCentral South University 中南大学湘雅二医院病理科中南大学湘雅二医院检验科中南大学基础医学院免疫系中南大学湘雅二医院放射科

U rogenital Chlamydia trachomatis infection is one of the most common bacterial sexually transmitted diseases globally.Untreated C.trachomatis infections can ascend to the upper genital tract and establish a series of severe complications.Previous studies using C3 and C5 mice models demonstrated that C3-independent activation of C5 occurred during C.trachomatis infection.H owever,the mechanism of how chlamydial infection activates C5 in the absence of C3 has yet to be elucidated.To delineate interactions between C5 and chlamydial infection,cleavage products in a co-incubation system containing purified human C5 and C.trachomatis-HeLa229 cell lysates were analyzed,and a novel cleavage pattern of C5 activation induced by C.trachomatis infection was identified.C5 was cleaved efficiently at the previously unidentified site K970,but was cleaved poorly at site R751.C5 b was modified to C5 bCt,which later formed C5 bCt-9,which had enhanced lytic ability compared with C5 b-9.The chlamydial serine protease CPAF contributed to C3-independent C5 activation during C.trachomatis infection.nafamostat mesylate,a serine protease inhibitor with a good safety profile,had a strong inhibitory effect on C5 activation induced by chlamydial infection.These discoveries reveal the mechanism of C3-independent C5 activation induced by chlamydial infection,and furthermore provide a potential therapeutic target and drug for preventing tubal fibrosis caused by chlamydial infection.

关键词： Chlamydia trachomatis infection complement C5 C5 convertase CPAF nafamostat mesylate

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