Optimizing ganciclovir and valganciclovir dosing regimens in pediatric patients with cytomegalovirus infection: a spotlight on therapeutic drug monitoring

by Selleckchem | Mar 10 2023

Introduction: Infants and immunocompromised children with cytomegalovirus (CMV) infection have significant morbidity and mortality. Ganciclovir (GCV) and its oral prodrug valganciclovir (VGCV) are the major antiviral options of choice for the prophylaxis and treatment of CMV infection. However, with the currently recommended dosing regimens used in pediatric patients, large intra- and inter-individual variability of pharmacokinetic (PK) parameters and exposure are observed.

Areas covered: This review describes the PK and pharmacodynamic (PD) characteristics of GCV and VGCV in pediatrics. Moreover, the role of therapeutic drug monitoring (TDM) and current clinical practice for GCV and VGCV dosing regimens optimization in pediatrics are discussed.

Expert opinion: GCV/VGCV TDM has shown the potential value to improve the benefit/risk ratio in pediatrics when using the therapeutic ranges derived from adults. However, well-designed studies are required to evaluate the relationship of TDM with clinical outcomes. Furthermore, studies to explore the children-specific dose-response-effect relationships will be helpful to facilitate the TDM practice. In the clinical setting, optimal sampling methods such as limited sampling strategies for pediatrics can be used in TDM and intracellular ganciclovir triphosphate may be used as an alternative TDM marker.

Comments：

Cytomegalovirus (CMV) infection can be particularly severe in infants and immunocompromised children, and ganciclovir (GCV) and valganciclovir (VGCV) are the primary antiviral agents used for prophylaxis and treatment. However, pediatric patients exhibit significant variability in pharmacokinetic (PK) parameters and exposure with currently recommended dosing regimens. This review discusses the PK and pharmacodynamic (PD) characteristics of GCV and VGCV in pediatrics, as well as the role of therapeutic drug monitoring (TDM) and current clinical practice for optimizing dosing regimens.

TDM has the potential to improve the benefit/risk ratio of GCV/VGCV use in pediatrics, but well-designed studies are necessary to evaluate the relationship between TDM and clinical outcomes. In addition, children-specific dose-response-effect relationships need to be explored to facilitate TDM practice. Optimal sampling methods, such as limited sampling strategies, can be used in TDM for pediatrics. Intracellular ganciclovir triphosphate may also be used as an alternative TDM marker.

In conclusion, TDM has shown promise in improving the efficacy and safety of GCV/VGCV use in pediatric patients. Future studies should focus on establishing pediatric-specific dosing regimens, exploring the dose-response-effect relationship, and evaluating the clinical impact of TDM-guided dosing. Optimal sampling strategies and alternative TDM markers may further facilitate TDM in pediatrics.