Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high pharmacokinetic (PK) interindividual variability and PK data are scarce, especially in paediatric stem cell transplant (SCT) recipients. We sought to determine the optimal GCV and VGCV dosing in transplanted children. Methods:We conducted a single-centre retrospective population PK (POPPK) study of IV GCV and enteral VGCV in paediatric solid organ transplant (SOT) and SCT recipients. We included children who were transplanted and had available plasma GCV concentrations, done per standard of care. POPPK analysis was performed using a nonlinear mixed effects modelling approach with NONMEM. Optimal dosing was determined based on the achievement of the surrogate efficacy target: GCV 24 h area under the concentration-time curve (AUC 0-24h ) of 40-60 mg.h.L −1 .Results: Fifty children with a median [range] age of 7.5 years [0.5-17.4] contributed 580 PK samples. A two-compartment model with first-order absorption with a lag time and first-order elimination fit the data well. Creatinine clearance and body weight (WT) were significant covariates for GCV clearance (CL); and WT for the volumes of distribution. IV GCV 15-20 mg.kg −1 .day −1 divided every 12 hours achieved the highest probability of target achievement (PTA) (33.0-33.8%). Enteral VGCV 30 and 40 mg.kg −1 .day −1 divided every 12 hours in children 0-<6 years, and 6-18 years, respectively, achieved the highest PTA (29.1-33.0%). Conclusion:This is the first POPPK model developed in children with either SOT or SCT. Concentration target achievement was low, suggesting a potential benefit for therapeutic drug monitoring to ensure optimal exposure.

A 67‐year‐old man was admitted to the emergency department about 5 h after deliberate self‐poisoning with 300 mg of Apixaban. The clinical examination did not show any organ dysfunctions or haemorrhagic signs, and the patient's life was not in danger. The first analysis, upon admission, showed a concentration of 2655 μg l−1 of Apixaban. The Cmax was observed 17 h after the intake (3654 μg l−1), about four times the classical Tmax value (median [range]: 4 h [2–4]). The Apixaban was then eliminated following a first order elimination with a calculated half‐life of 10.8 h. The anti‐Xa activity seems to be linearly related to concentration up to 4000 μg l−1. This report suggests that the use of activated charcoal should be effective up to 17 h after a massive intake.

Ganciclovir and valganciclovir 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 ganciclovir and valganciclovir 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 average 24‐hour area under the concentration‐time curve (AUC0–24h) seems to be the best predictor of efficacy and toxicity. The benefit of 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 with this aim and may be used in clinical practice for the AUC‐based individual dose adjustment of ganciclovir and valganciclovir.