%0 Journal Article
%A Huurneman, Luc J
%A Neely, Michael
%A Veringa, Anette
%A Docobo Pérez, Fernando
%A Ramos-Martin, Virginia
%A Tissing, Wim J
%A Alffenaar, Jan-Willem C
%A Hope, William
%T Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy.
%D 2016
%@ 0066-4804
%U http://hdl.handle.net/10668/2531
%X Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC50) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC50)/15.4 predicted terminal galactomannan (P= 0.003), and a ratio of >6 suggested a lower terminal galactomannan level (P= 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.
%K Antifúngicos
%K Área bajo la curva
%K Aspergilosis
%K Mananos
%K Probabilidad
%~