Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis.
Molecules
; 27(6)2022 Mar 14.
Article
in English
| MEDLINE | ID: covidwho-1742556
ABSTRACT
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 13C6-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 (t1/2) 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Tandem Mass Spectrometry
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal subject:
Biology
Year:
2022
Document Type:
Article
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