The tyrosine kinase inhibitor (TKI) imatinib was rationally designed to target BCR-ABL1 which is constitutively activated in chronic myeloid leukemia (CML). Following the tremendous success in adults, imatinib also became licensed for treatment of CML in minors. The rarity of pediatric CML hampers the conduction of formal trials. Thus, imatinib is still the single TKI approved for CML treatment in childhood. Areas covered: This review attempts to provide an overview of the literature on pharmacology, pharmacokinetic, and pharmacogenetic of imatinib concerning pediatric CML treatment. Articles were identified through a PubMed search and by reviewing abstracts from relevant hematology congresses. Additional information was provided from the authors' libraries and expertise and from our own measurements of imatinib trough plasma levels in children. Pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. Expert commentary: TKI response rates vary among different individuals and pharmacokinetic variables all can influence CML treatment success. Adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring.
Keywords: Imatinib; OCT-1-influx; P-glycoprotein-efflux; alpha 1-acid glycoprotein; children; compliance; cytochrome P450 3A4/5; dose; drug monitoring; drug–drug/food–drug interactions; generics; infants; pharmacokinetics; teenagers; trough level.