School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Korea.
Molecules. 2022 Mar 14;27(6):1881. doi: 10.3390/molecules27061881.
Nafamostat, a synthetic serine protease inhibitor, has been used for the treatment of inflammatory diseases such as pancreatitis. Recently, an increasing number of studies have shown the promising antiviral effects of nafamostat for the treatment of coronavirus disease-19 (COVID-19). This study aimed to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and to characterize the pharmacokinetics of nafamostat in rats. Nafamostat in the rat plasma was extracted by solid phase extraction, and C-nafamostat was used as an internal standard. The quantification limit of nafamostat in the rat plasma was 0.5 ng/mL. The LC-MS/MS method was fully validated and applied to characterize the pharmacokinetics of nafamostat in rats. Following intravenous injection (2 mg/kg), nafamostat in the plasma showed a multiexponential decline with an average elimination half-life (t) of 1.39 h. Following oral administration of nafamostat solutions (20 mg/kg) in 10% dimethyl sulfoxide (DMSO) and in 10% DMSO with 10% Tween 80, nafamostat was rapidly absorbed, and the average oral bioavailability was 0.95% and 1.59%, respectively. The LC-MS/MS method and the pharmacokinetic information of nafamostat could be helpful for the further preclinical and clinical studies of nafamostat.
那屈肝素钙，一种合成丝氨酸蛋白酶抑制剂，已被用于治疗胰腺炎等炎症性疾病。最近，越来越多的研究表明那屈肝素钙在治疗 2019 冠状病毒病（COVID-19）方面具有有前景的抗病毒作用。本研究旨在开发一种新的液相色谱-串联质谱（LC-MS/MS）分析方法，并研究那屈肝素钙在大鼠体内的药代动力学特征。大鼠血浆中的那屈肝素钙经固相萃取提取，以 C-那屈肝素钙作为内标。大鼠血浆中那屈肝素钙的定量下限为 0.5ng/mL。该 LC-MS/MS 方法经过充分验证，并用于研究那屈肝素钙在大鼠体内的药代动力学特征。静脉注射（2mg/kg）后，那屈肝素钙在血浆中呈多指数衰减，平均消除半衰期（t）为 1.39h。以 10%二甲基亚砜（DMSO）和 10%DMSO 中添加 10%聚山梨酯 80 的溶液口服给予那屈肝素钙（20mg/kg）后，那屈肝素钙迅速吸收，平均口服生物利用度分别为 0.95%和 1.59%。该 LC-MS/MS 方法和那屈肝素钙的药代动力学信息有助于进一步开展那屈肝素钙的临床前和临床研究。
