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The Vascular Endothelial Growth Factor (VEGF) in Ischemiafor Vascular Angiogenesis (VIVA) trial was a double‐blind, placebo‐controlled, phase II clinical trial designed to evaluate the safety, efficacy, and pharmacokinetics of combinedintracoronary and intravenous infusions of recombinant human vascular endothelial growth factor (rhVEGF₁₆₅) for therapeutic angiogenesis. This study describes the use of a mechanism‐based model to characterize the nonlinear kinetics observed after intravenous administration of rhVEGF₁₆₅. The model predicts that rhVEGF₁₆₅ distribution occurs through both saturable binding to high‐affinity receptors and reversible interactions with low‐affinity binding sites.

In this trial, rhVEGF₁₆₅ was administered to patients with coronary artery disease at a dose rate of 17 or 50 ng/kg/min by means of intracoronary infusion for 20 minutes, followed by three 4‐hour …