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dc.contributor.authorLányi, Katalin
dc.contributor.authorMonostory, Katalin
dc.contributor.authorSteinmetzer, Torsten
dc.contributor.authorJerzsele, Ákos
dc.contributor.authorPászti-Gere, Erzsébet
dc.date.accessioned2024-09-26T10:35:23Z
dc.date.available2024-09-26T10:35:23Z
dc.date.issued2023
dc.identifier.citationLányi K, Monostory K, Steinmetzer T, Jerzsele Á, Pászti-Gere E. In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes. Biomedicines. 2023 Feb 23;11(3):682. doi: 10.3390/biomedicines11030682en_US
dc.identifier.urihttp://hdl.handle.net/10832/4088
dc.description.abstractType II transmembrane serine proteases represent pharmacological targets for blocking entry and spread of influenza or coronaviruses. In this study, the depletion rates of the 3-amidinophenylalanine (3-APhA)-derived matriptase/TMPRSS2 inhibitors MI-463, MI-472, MI-485 or MI-1900 were determined by LC-MS/MS measurements over a period of 300 min using suspensions of rat, dog and cynomolgus monkey primary hepatocytes. From these in vitro pharmacokinetic (PK) experiments, intrinsic clearance values (Clint) were evaluated, and in vivo pharmacokinetic parameters (hepatic clearance, hepatic extraction ratio and bioavailability) were predicted. It was found that rat hepatocytes were the most active in the metabolism of 3-APhA derivatives (Clint 31.9-37.8 mL/min/kg), whereas dog and monkey cells displayed somewhat lower clearance of these compounds (Clint 6.6-26.7 mL/min/kg). These data support elucidation of important PK properties of anti-TMPRSS2/anti-matriptase 3-APhAs using mammalian hepatocyte models and thus contribute to the optimization of lead compounds.en_US
dc.language.isoenen_US
dc.titleIn Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytesen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/biomedicines11030682


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