BackgroundCoronary stenting is associated with two major complications: subacute thrombosis and neointimal proliferation resulting in restenosis. Our hypothesis is that the biocom-patibility of metallic stents can be improved by coating with a polymer membrane that delivers agents that favorably modify the local arterial microenvironment. This study evaluates the kinetics, distribution, and bioactivity of the model drug for-skolin delivered to the local arterial wall by a polyurethane-coated removable metallic stent.Methods and ResultsStents were used in rabbit carotid arteries (n=20) for as long as 24 hours. The quantity of forskolin bound to the stent decreased exponentially with a half-life of 5.8 hours. Blood concentrations peaked at 140±39 pg/μL at 4 hours. The adjacent arterial media contained 60±39 ng/mg, which was 380- and 460-fold greater than the contralateral carotid media and the systemic blood, respectively (P<.0001). Media forskolin concentrations declined exponentially over time with a tissue half-life of 5.0 hours. Drug distributed throughout the vessel wall with decreasing gradients in the radial and axial dimensions consistent with a diffusion process. Removal of the stent was associated with a 100-fold decline in media forskolin concentration within 2 hours. Forskolin release was associated with a sustained 92% increase in carotid blood flow and a 60% decrease in local arterial resistance compared with coated control stents (P<.005). In another set of rabbits (n=14) using a carotid crush injury, flow-reduction model, forskolin prolonged the time to flow variation and occlusion by 12-fold compared with the use of bare metal stents and 5-fold compared with the use of polyurethane-coated stents (P<.0001).ConclusionsA polymer-coated metallic stent can deliver forskolin to the local arterial wall in high concentrations relative to the blood or other tissues. High local drug concentrations are dependent on maintaining stent-to-tissue gradients. The delivered drug is biologically active, demonstrating vasodilating and antiplatelet properties.