Abstract
Intracellular pharmacokinetics (PK) of activated drugs is a window to understanding the pharmacodynamics of prodrug-enzyme-ultrasound therapy. Herein PK of ZD2767D (i.e., activated drug) in the ZD2767P+CPG2+US system on A549, A549/DDP, SKOV3, and SKOV3/DDP cells were evaluated (A549/DDP and SKOV3/DDP were cisplatin-resistant sublines). The noncompartment model under extravascular input mode was deemed appropriate for evaluating drug level vs time curves; C(max), AUC(last), MRT(last), V(z), and Cl can reflect the PK feature, but t(1/2), AUC(inf), and MRT(inf) were irrational; higher accumulation and slower elimination characterized the PK mechanism of ZD2767P+CPG2+US; enhanced permeability and retention effect can be assessed with C(max), AUC(last), MRT(last), and t(last); ultrasound equivalently modulated C(max) and AUC(last) in sensitive and resistant cells. The experimental design and dose proportionality were discussed.