Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis
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 aime...
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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/6/1881 |
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| author | Hyeon Seok Oh Taehyung Kim Dong-Hyeon Gu Tae Suk Lee Tae Hwan Kim Soyoung Shin Beom Soo Shin |
| author_facet | Hyeon Seok Oh Taehyung Kim Dong-Hyeon Gu Tae Suk Lee Tae Hwan Kim Soyoung Shin Beom Soo Shin |
| author_sort | Hyeon Seok Oh |
| collection | DOAJ |
| description | 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 <sup>13</sup>C<sub>6</sub>-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<sub>1/2</sub>) 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. |
| first_indexed | 2024-03-09T13:10:38Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:10:38Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6c261f0fccad4241ad55b2b357a3e5162023-11-30T21:42:41ZengMDPI AGMolecules1420-30492022-03-01276188110.3390/molecules27061881Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS AnalysisHyeon Seok Oh0Taehyung Kim1Dong-Hyeon Gu2Tae Suk Lee3Tae Hwan Kim4Soyoung Shin5Beom Soo Shin6School of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaCollege of Pharmacy, Daegu Catholic University, Gyeongsan 38430, KoreaCollege of Pharmacy, Wonkwang University, Iksan 54538, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaNafamostat, 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 <sup>13</sup>C<sub>6</sub>-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<sub>1/2</sub>) 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.https://www.mdpi.com/1420-3049/27/6/1881nafamostatCOVID-19LC-MS/MSpharmacokineticsbioavailability |
| spellingShingle | Hyeon Seok Oh Taehyung Kim Dong-Hyeon Gu Tae Suk Lee Tae Hwan Kim Soyoung Shin Beom Soo Shin Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis Molecules nafamostat COVID-19 LC-MS/MS pharmacokinetics bioavailability |
| title | Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis |
| title_full | Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis |
| title_fullStr | Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis |
| title_full_unstemmed | Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis |
| title_short | Pharmacokinetics of Nafamostat, a Potent Serine Protease Inhibitor, by a Novel LC-MS/MS Analysis |
| title_sort | pharmacokinetics of nafamostat a potent serine protease inhibitor by a novel lc ms ms analysis |
| topic | nafamostat COVID-19 LC-MS/MS pharmacokinetics bioavailability |
| url | https://www.mdpi.com/1420-3049/27/6/1881 |
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