A systematic review on clinical pharmacokinetics and pharmacodynamics of antiangiogenic tyrosine kinase inhibitors (TKIs) with high TDM scores

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Tyrosine kinase inhibitor (TKI) drugs are used to treat various cancer types. This systematic review evaluates the published pharmacokinetic (PK) and pharmacodynamic (PD) parameters of TKI drugs with high therapeutic drug monitoring (TDM) scores in humans. A comprehensive computerized literature search of four internet databases was carried out until July 2025 for sunitinib, pazopanib, sorafenib, axitinib, and cabozantinib, and it provided 3192 articles, of which 56 met the inclusion criteria by providing human PK and related PD information. The exposure of TKI drugs generally increases with the dose escalation, as reflected by higher area under the curve from zero to infinity (AUC0–∞) and maximum plasma concentration (Cmax). In pediatric patients, sunitinib showed dose-dependent increases in exposure. Cabozantinib 140 mg showed higher exposure under fed versus fasted conditions, with AUC0–∞ increasing from 60,700 to 95,200 ng·h/ml and Cmax from 505 to 709 ng/ml. In pediatric gastrointestinal stromal tumor patients, sunitinib exhibited a large apparent volume of distribution (V/F) 3160 L, indicating extensive tissue distribution. This review summarizes clinical PK, drug–drug interaction studies, effects of dosage form on PK, and corresponding PD parameters of TKI drugs supporting PK models development for optimizing dosing regimens. www.crd.york.ac.uk/prospero identifier is CRD420251110777.

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