The importance of PK/PD data-key biological answers needed to evaluate the success of potential cancer therapeutics.

摘要

The preclinical pharmacokinetic (PK)-pharmacody-namic (PD) data generated for pazopanib identified in vivo concentrations resulting in the inhibition of target receptors and pharmacological effects consistent with inhibition of the target receptors (1). We established that sustained inhibition of vascular endothelial growth factor receptor (VEGFR) 2 in vivo was required for maximum anti-angiogenic and anti-tumor effects and, as such, trough plasma concentration will be the key driver for biological activity of pazopanib and other VEGFR inhibitors. Based on preclinical experiments, we proposed that trough concentration (C24h) of ~40 uM pazopanib is required for optimal biological effects.