TY - JOUR
T1 - Therapeutic drug monitoring of ganciclovir
T2 - Where are we?
AU - Märtson, Anne-Grete
AU - Edwina, Angela E
AU - Kim, Hannah Yejin
AU - Knoester, Marjolein
AU - Touw, Daan J
AU - Sturkenboom, Marieke G G
AU - Alffenaar, Jan-Willem C
N1 - Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - PURPOSE: Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such as myelosuppression, which often leads to therapy cessation. Underdosing, as an attempt to prevent side effects, can lead to drug resistance and therapy failure. Therapeutic drug monitoring (TDM) has been used to overcome these problems. The purpose of this narrative review was to give an overview of ganciclovir TDM, available assays, population pharmacokinetic models and discuss the current knowledge gaps.METHODS: For this narrative review a non-systematic literature search was done on the PubMed database in April 2021. The following search terms were used: ganciclovir, valganciclovir, pharmacokinetics, pharmacodynamics, population pharmacokinetics, therapeutic drug monitoring, bioassay, LC-MS/MS, liquid chromatography, chromatography, spectrophotometry, toxicity. In addition, the reference lists of the included articles were screened.RESULTS: The most common bioanalysis method identified was liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). There are different models presenting ganciclovir IC50, however establishing a pharmacokinetic/pharmacodynamic (PK/PD) target for ganciclovir based on preclinical data is difficult, as there are no studies combining dynamic drug exposure in relation to inhibition of viral replication. The data on ganciclovir TDM show large inter-individual variability, indicating that TDM may play a role in modifying the dose to reduce toxicity and prevent treatment failure related to low concentrations. The main hurdle for implementing TDM is the lack of robust data to define a therapeutic window.CONCLUSION: Although the pharmacokinetics (PK) involved are relatively well-described, both the pharmacodynamics (PD) and PK/PD relationship are not. This is because the studies conducted to date have mainly focused on estimating ganciclovir exposure, and due to the limited therapeutic options for CMV infections, future studies on ganciclovir are warranted.
AB - PURPOSE: Ganciclovir is the mainstay of therapy for the prophylaxis and treatment of cytomegalovirus. However, therapy with this antiviral agent is hindered by side effects such as myelosuppression, which often leads to therapy cessation. Underdosing, as an attempt to prevent side effects, can lead to drug resistance and therapy failure. Therapeutic drug monitoring (TDM) has been used to overcome these problems. The purpose of this narrative review was to give an overview of ganciclovir TDM, available assays, population pharmacokinetic models and discuss the current knowledge gaps.METHODS: For this narrative review a non-systematic literature search was done on the PubMed database in April 2021. The following search terms were used: ganciclovir, valganciclovir, pharmacokinetics, pharmacodynamics, population pharmacokinetics, therapeutic drug monitoring, bioassay, LC-MS/MS, liquid chromatography, chromatography, spectrophotometry, toxicity. In addition, the reference lists of the included articles were screened.RESULTS: The most common bioanalysis method identified was liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). There are different models presenting ganciclovir IC50, however establishing a pharmacokinetic/pharmacodynamic (PK/PD) target for ganciclovir based on preclinical data is difficult, as there are no studies combining dynamic drug exposure in relation to inhibition of viral replication. The data on ganciclovir TDM show large inter-individual variability, indicating that TDM may play a role in modifying the dose to reduce toxicity and prevent treatment failure related to low concentrations. The main hurdle for implementing TDM is the lack of robust data to define a therapeutic window.CONCLUSION: Although the pharmacokinetics (PK) involved are relatively well-described, both the pharmacodynamics (PD) and PK/PD relationship are not. This is because the studies conducted to date have mainly focused on estimating ganciclovir exposure, and due to the limited therapeutic options for CMV infections, future studies on ganciclovir are warranted.
U2 - 10.1097/FTD.0000000000000925
DO - 10.1097/FTD.0000000000000925
M3 - Review article
C2 - 34610621
VL - 44
SP - 138
EP - 147
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
SN - 0163-4356
IS - 1
ER -