RT Journal Article
T1 Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy.
A1 Huurneman, Luc J
A1 Neely, Michael
A1 Veringa, Anette
A1 Docobo Pérez, Fernando
A1 Ramos-Martin, Virginia
A1 Tissing, Wim J
A1 Alffenaar, Jan-Willem C
A1 Hope, William
K1 Antifúngicos
K1 Área bajo la curva
K1 Aspergilosis
K1 Mananos
K1 Probabilidad
AB 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.
PB American Society for Microbiology
SN 0066-4804
YR 2016
FD 2016-04-25
LK http://hdl.handle.net/10668/2531
UL http://hdl.handle.net/10668/2531
LA en
NO Huurneman LJ, Neely M, Veringa A, Docobo Pérez F, Ramos-Martin V, Tissing WJ, et al. Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy. Antimicrob. Agents Chemother.2016; 60(4):2336-42
NO Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 7, 2025