Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads

Martson, Anne-Grete ORCID: 0000-0001-6478-1959, Sturkenboom, Marieke GG, Knoester, Marjolein, van der Werf, Tjip S, Alffenaar, Jan-Willem C, Hope, William ORCID: 0000-0001-6187-878X and Consortium, GATEWAY-1 Study
(2021) Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 77 (2). pp. 466-473.

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<h4>Background</h4>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.<h4>Objectives</h4>To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ganciclovir in transplant recipients.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: GATEWAY-1 Study Consortium, Humans, Cytomegalovirus, Ganciclovir, Antiviral Agents, Viral Load, Valganciclovir
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 07 Jun 2022 09:18
Last Modified: 18 Jan 2023 21:00
DOI: 10.1093/jac/dkab419
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