Pharmacokinetics, pharmacodynamics and therapeutic drug monitoring of valganciclovir and ganciclovir in transplantation.

Ganciclovir (GCV) and valganciclovir (VGCV) are first choice drugs for the prevention and treatment of cytomegalovirus infection and disease in solid organ and stem cell transplant recipients. Only a few studies on the pharmacokinetics and exposure/efficacy or exposure/safety relationships of ganciclovir and valganciclovir in transplant recipients have been published so far and there are still controversies about the exposure parameter to use for therapeutic drug monitoring (TDM). We performed an extensive literature review of the clinical pharmacokinetics data, the exposure/effect relationships in terms of efficacy and safety and the available tools for valganciclovir and ganciclovir TDM in adults and pediatrics transplant recipients. The pharmacokinetics of GCV and VGCV is well described in adults and children and a high interindividual variability is commonly observed. In contrast, the drug pharmacodynamics has been poorly described in adults and barely in children. The AUC0-24h seems to be the best predictor of efficacy and toxicity. The benefit of the TDM remains controversial in adult patients but should be considered in children due to higher interindividual variability and lower probability of target attainment. Several Bayesian estimators based on limited sampling strategies have been developed in this aim and may be used in clinical practice for the AUC-based individual dose adjustment of ganciclovir and valganciclovir.