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Background <p>The Borna disease virus 1 (BoDV-1) causes a rare, but severe form of encephalitis in Germany, characterized by rapid progression, late diagnosis, and a high case fatality. Therapy is experimental and recommendations are lacking. Favipiravir (FPV) suppresses BoDV-1 replication in vitro and has been used in a handful of BoDV-1 patients within individual treatment attempts, but little is known about the drug´s pharmacokinetics in encephalitis.</p> Methods <p>To monitor and therefore optimize experimental FPV treatment, we established a liquid chromatography tandem&#xa0;mass spectroscopy (LC–MS/MS) assay for serum and cerebrospinal fluid (CSF), and analyzed stored specimens of two patients with BoDV-1 encephalitis in the context of therapeutic drug monitoring as a pilot investigation.</p> Results <p>We demonstrate for the first time that orally administered FPV reaches the CSF in BoDV-1 encephalitis. However, the half-maximal inhibitory concentration (IC50) for BoDV-1 was met only in one patient, raising questions on significantly higher dosing and/or alternative formulations for effective treatment.</p> Conclusion <p>In conclusion, monitoring experimental FPV therapy in BoDV-1 encephalitis is feasible and should be performed continuously. Future prospective in-depth (multicenter) studies should include more patients and focus on dose-finding, dose–response relationships, and define a therapeutic index to improve outcomes of this so far nearly uniformly fatal disease.</p>

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First therapeutic drug monitoring of experimental favipiravir in Borna disease virus 1 (BoDV-1) encephalitis patients reveals significant gaps in antiviral treatment: a pilot investigation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月4日

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  • Michael Paal,
  • Katharina Habler,
  • Alice Ewert,
  • Michael Vogeser,
  • Leonie Grosse,
  • Victoria Lieftüchter,
  • Simone C. Tauber,
  • Johannes Schiefer,
  • Petra Allartz,
  • Dennis Tappe,
  • Kirsten Pörtner

摘要

Background

The Borna disease virus 1 (BoDV-1) causes a rare, but severe form of encephalitis in Germany, characterized by rapid progression, late diagnosis, and a high case fatality. Therapy is experimental and recommendations are lacking. Favipiravir (FPV) suppresses BoDV-1 replication in vitro and has been used in a handful of BoDV-1 patients within individual treatment attempts, but little is known about the drug´s pharmacokinetics in encephalitis.

Methods

To monitor and therefore optimize experimental FPV treatment, we established a liquid chromatography tandem mass spectroscopy (LC–MS/MS) assay for serum and cerebrospinal fluid (CSF), and analyzed stored specimens of two patients with BoDV-1 encephalitis in the context of therapeutic drug monitoring as a pilot investigation.

Results

We demonstrate for the first time that orally administered FPV reaches the CSF in BoDV-1 encephalitis. However, the half-maximal inhibitory concentration (IC50) for BoDV-1 was met only in one patient, raising questions on significantly higher dosing and/or alternative formulations for effective treatment.

Conclusion

In conclusion, monitoring experimental FPV therapy in BoDV-1 encephalitis is feasible and should be performed continuously. Future prospective in-depth (multicenter) studies should include more patients and focus on dose-finding, dose–response relationships, and define a therapeutic index to improve outcomes of this so far nearly uniformly fatal disease.