Revisiting Acyclovir Dosing for Adult Viral Encephalitis Using a Full Bayesian LeiCNS PBPK Modeling Approach
The standard regimen (10 mg/kg TID) achieved the 50%fT > IC<sub>50</sub> target but failed to consistently meet the C<sub>min</sub> > IC<sub>50</sub> target, particularly for VZV. Alternative regimens of increasing the dosing frequency to QID or extending infusion durations to 1.5 h or 2 h improved efficacy while maintaining safety. Prolonged infusion durations reduced peak plasma concentration thus lowered toxicity risks CONCLUSIONS: The Bayesian CNS PBPK modeling approach demonstrated robust predictive capacity for CNS PK. Current acyclovir dosing regimens may be inadequate for treating HSV and VZV encephalitis. Alternative dosing strategies involving increased frequency or extended infusion durations appear more effective and safer. Future efforts should focus on refining the PK/pharmacodynamic (PD) relationship between acyclovir exposure and antiviral efficacy to improve therapeutic outcomes.
Authors
- Elizabeth C. M. de Lange (ORCID: https://orcid.org/0000-0001-8303-1117)
- Ming Sun (ORCID: https://orcid.org/0000-0001-8018-1152)
- Tingjie Guo (ORCID: https://orcid.org/0000-0002-7892-6220)
- Anne‐Grete Märtson (ORCID: https://orcid.org/0000-0001-6478-1959)
- Martijn L. Manson (ORCID: https://orcid.org/0000-0002-5508-8615)
- Jacob Bodilsen (ORCID: https://orcid.org/0000-0002-7398-814X)
Institutions
- Aalborg University Hospital (DK)
- Centre for Human Drug Research (NL)
- European Society of Clinical Microbiology and Infectious Diseases (CH)
- Aalborg University (DK)
Publication Details
- Journal
- Clinical Pharmacokinetics
- Published
- 2025-07-13
- DOI
- https://doi.org/10.1007/s40262-025-01545-w
- Citations
- 2
- Primary Topic
- Viral Infections and Immunology Research
- Type
- article
- Field-Weighted Citation Impact
- 2.78
Funders
- China Scholarship Council