Contribution of population pharmacokinetics to dose optimization of ganciclovir/valganciclovir in solid organ transplant patients.
Padulles A, Colom H, et al.Antimicrobial Agents & Chemotherapy 2016; 60(4):1992-2002
Aims
To investigate whether a Bayesian prediction model can optimize Ganciclovir-Valganciclovir (GCV-VGCV) dosing in solid organ transplant recipients.
Interventions
Patients were randomized to receive either GCV-VGCV according to the manufacturer’s dosing recommendations (group A), versus adjusted dosing based on target exposures using a Bayesian prediction model (group B).
Participants
60 kidney, liver, and heart transplant recipients aged ≥18 years of age, treated with GCV or VGCV as either prophylaxis or treatment of cytomegalovirus (CMV) infection.
Outcomes
The primary outcomes measured were the percentage of patients achieving target area under the curve (AUC) values between 40-50µg.h/ml, exposures on days 30, 60, and 90, and the time needed to achieve target AUC values. Secondary measured outcomes were measurements of time to viral clearance, recurrence of CMV infection, and incidence of late-onset CMV infection.
Follow-up
6 months
CET Conclusions
The RCT compared the efficacy of two treatment strategies for solid organ transplant recipients with CMV infection. Sixty kidney, liver and heart transplant recipients received ganciclovir-valganciclovir according to the manufacturer’s dosing recommendations (based on Cockcroft-Gault-calculated creatinine clearance and body weight) or according to a pharmacokinetics (PPK) modelling approach which did not include body weight. The primary endpoint was defined as a 40% or higher superiority margin in the number of patients reaching the AUC target of 40–50 µg·h/ml. The sample size was sufficient to provide 80% power. There was no description of how patients were allocated to groups and whether allocation was concealed. The PKK modelling approach led to a significantly higher percentage of AUC values within target range (65.9% versus 19.2%) and the time to reach target AUC was also significantly shorter.
Data analysis
Modified intention-to-treat analysis
Trial registration
EudraCT no. 2010-021433-32; ClinicalTrials.gov - NCT01446445