This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Valganciclovir, the oral prodrug of ganciclovir, is an antiviral medication used clinically for prophylaxis and treatment of serious DNA viral infections. These infections typically occur in persons who are immunocompromised, such as those infected with HIV or those who have undergone transplantation. Published data on ganciclovir pharmacokinetics in children following the administration of valganciclovir are lacking, although the drug is commonly given to pediatric solid organ and stem cell transplant recipients for prophylaxis. As a result of the lack of pharmacokinetic data, valganciclovir dosing in this patient population is highly variable. Traditional pharmacokinetic studies have been particularly challenging to conduct in pediatric populations secondary to the need for frequent, fixed-time blood sampling, and collection of large amounts of blood over a prolonged period of time. We are proposing a novel population pharmacokinetic study which has fewer design criteria than traditional approaches and can be easily adapted to the clinical setting (e.g. subjects can be patients currently being treated with the drug of interest). Blood sampling for a population pharmacokinetic study is sparse, requiring only a few randomly collected samples per subject, and collection times are flexible. Sparsely collected data can then be combined and intensively collected data in a small number of subjects to determine the best pharmacokinetic model for the data. Our objective is to use this study design and a nonlinear mixed-effects modeling approach to determine the pharmacokinetic parameters of ganciclovir in pediatric transplant patients prescribed valganciclor for prophylaxis. This design will also allow us to evaluate patient-specific co-variates (e.g. age, weight, sex, body surface area, renal function) for their influence on ganciclovir pharmacokinetic parameters. Overall the study will provide much needed clinical data on the behavior of ganciclovir following administration of valganciclovir to pediatric transplant recipients. In addition, these data should enable us to design future clinical studies with valganciclovir in this population in order to assess relationships between ganciclovir exposure and clinical response, and to evaluate methods of individualizing valganciclovir dosing.
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