Target Drug Exposure Attainment in Children: How to Get from Better to Best
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COMMENTARY
Target Drug Exposure Attainment in Children: How to Get from Better to Best Robert B. Flint1,2 · Karel Allegaert2,3,4
© The Author(s) 2020
1 Introduction The maturational physiology of children is reflected in more complex dosing regimens to attain target exposure throughout pediatric life [1]. For multiple drugs, therapeutic drug monitoring (TDM) may support the optimization of pharmacotherapy if the following requirements are met: (1) a narrow therapeutic range, (2) a large variability, (3) a known concentration–effect relationship, and (4) absence of measurable effect. Model-informed precision dosing (MIPD), the next step for TDM, has recently gained more attention as it may serve as a powerful tool to help individualize dosing [2]. In particular, pediatric pharmacotherapy may benefit from the development of such clinical decision support (CDS) and move beyond complex dosing regimens to even more personalized dosing. In this issue of the journal, Hartman et al. [3] evaluate target attainment during TDM of vancomycin, gentamicin, and tobramycin dosed according to model-based dosing guidelines for critically ill neonates and children. Despite this, the authors still observed a large proportion of both sub- and supratherapeutic concentrations for all three drugs. We very much appreciate their initiative in evaluating target attainment following the implemented simplification of the more This comment refers to the article available at https://doi. org/10.1007/s40272-020-00400-8. * Karel Allegaert [email protected] 1
Department of Pediatrics, Division Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands
2
Department of Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands
3
Department of Development and Regeneration, p/a Neonatal Intensive Care Unit, UZ Leuven, Herestraat 49, 3000 Leuven, Belgium
4
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
complex dosage regimen suggested in the published population pharmacokinetic (PK) models [4, 5]. Their elegant design using data collected for TDM may be an inspiration for improved evaluation of pharmacotherapy for other drugs, as no additional burden was needed. In this commentary, we would like to stress that such efforts are—at best—part of a target exposure improvement approach: how do we get from better to best? This relates to the “best target selection” and “best target attainment.”
2 Selection of the Best Target Hartman et al. [3] used vancomycin trough concentrations as a surrogate target for an area under the plasma concentration–time curve (AUC)0–24h > 400 to determine adequate therapy, although the target trough corresponding to an AUC 0–24h of 400 depends on the dosing interval and individual clearance [6]. Allegaert et al. [7] illustrated that a certain daily dose for an AUC of 4 000–24h divided by 12-, 8-, and 6-h intervals corresponds to a trough steady state concentration of 11.3, 13.0, and 14.0 mg/L, respectively. Model-based e
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