Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

Julie M. Janssen, Thomas P.C. Dorlo, Neeltje Steeghs, Jos H. Beijnen, Lidwien M. Hanff, Natasha K.A. van Eijkelenburg, Jasper van der Lugt, C. Michel Zwaan, Alwin D.R. Huitema

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)

Abstract

In recent years new targeted small molecule kinase inhibitors have become available for pediatric patients with cancer. Relationships between drug exposure and treatment response have been established for several of these drugs in adults. Following these exposure–response relationships, pharmacokinetic (PK) target minimum plasma rug concentration at the end of a dosing interval (Cmin) values to guide therapeutic drug monitoring (TDM) in adults have been proposed. Despite the fact that variability in PK may be even larger in pediatric patients, TDM is only sparsely applied in pediatric oncology. Based on knowledge of the PK, mechanism of action, molecular driver, and pathophysiology of the disease, we bridge available data on the exposure–efficacy relationship from adults to children and propose target Cmin values to guide TDM for the pediatric population. Dose adjustments in individual pediatric patients can be based on these targets. Nevertheless, further research should be performed to validate these targets.

Original languageEnglish
Pages (from-to)494-505
Number of pages12
JournalClinical Pharmacology and Therapeutics
Volume108
Issue number3
DOIs
Publication statusPublished - 1 Sept 2020

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