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 (C_min) 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 C_min 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.

中文翻译：

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小儿肿瘤学中小分子激酶抑制剂治疗药物监测的药代动力学目标。

近年来，新的靶向小分子激酶抑制剂已可用于患有癌症的儿科患者。已针对成人中的几种此类药物建立了药物暴露与治疗反应之间的关系。遵循这些暴露-反应关系，已经提出了在给药间隔（C _min）值结束时药代动力学（PK）目标最低血浆地毯浓度，以指导成人治疗药物监测（TDM）。尽管事实是小儿患者的PK变异可能更大，但TDM仅很少应用于儿科肿瘤学。基于对疾病的PK，作用机制，分子驱动因素和病理生理学的了解，我们将成人与儿童之间的暴露-功效关系的可用数据进行桥接，并提出目标C指导小儿TDM的_最小值。个别儿科患者的剂量调整可以基于这些目标。尽管如此，应该进行进一步的研究以验证这些目标。