Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads

GATEWAY-1 Study Consortium, Anne-Grete Märtson*, Marieke G G Sturkenboom, Marjolein Knoester, Tjip S van der Werf, Jan-Willem C Alffenaar, William Hope

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Cytomegalovirus (CMV) can cause severe disease, including rejection in transplant recipients. Ganciclovir and its oral prodrug valganciclovir have been used as first-line therapy for CMV disease in transplant recipients. The exposure targets of ganciclovir are not exactly known, and toxicity and resistance have interfered with ganciclovir therapy.

OBJECTIVES: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ganciclovir in transplant recipients.

METHODS: We used patient data from a previous observational study on ganciclovir therapeutic drug monitoring (TDM) in prophylaxis and therapy. The ganciclovir concentrations and CMV viral loads were determined during routine clinical care. The PK/PD population modelling and simulations were done with non-parametric methodology using the Pmetrics program.

RESULTS: Eighty-five patients were included in the PK modelling. The final PK model was a two-compartment model with first-order absorption and elimination. A subset of 17 patients on CMV therapy were included in the PD modelling. A median of 4 (range 2-8) viral loads were obtained per patient. A simulation of 10 000 patients showed that an approximately 1 log10 reduction of CMV viral load will be observed after 12.5 days at the current recommended dose.

CONCLUSIONS: The developed linked PK/PD population model and subsequent PD simulations showed slow decline of CMV viral load and it appears that dosing of (val)ganciclovir in this study might have been inadequate to achieve fast reduction of viral load. It is clear that further studies are needed to specify the PD effects of ganciclovir by performing systematic measurements of both ganciclovir concentrations and CMV viral loads.

Original languageEnglish
Pages (from-to)466-473
Number of pages8
JournalThe Journal of antimicrobial chemotherapy
Volume77
Issue number2
DOIs
Publication statusPublished - 2-Feb-2022

Keywords

  • Antiviral Agents/therapeutic use
  • Cytomegalovirus
  • Ganciclovir/therapeutic use
  • Humans
  • Valganciclovir
  • Viral Load

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