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Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis.
Oh, Hyeon Seok; Kim, Taehyung; Gu, Dong-Hyeon; Lee, Tae Suk; Kim, Tae Hwan; Shin, Soyoung; Shin, Beom Soo.
Afiliação
  • Oh HS; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
  • Kim T; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
  • Gu DH; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
  • Lee TS; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
  • Kim TH; College of Pharmacy, Daegu Catholic University, Gyeongsan 38430, Korea.
  • Shin S; College of Pharmacy, Wonkwang University, Iksan 54538, Korea.
  • Shin BS; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Molecules ; 27(6)2022 Mar 14.
Article em En | MEDLINE | ID: mdl-35335247
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectrometria de Massas em Tandem / COVID-19 Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Espectrometria de Massas em Tandem / COVID-19 Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article