Kinetics of drugs delivery to the arteriall wall via polyurethane‐coated removable nitinol stent: Comparative study of two drugs

Abstract

Abstract Polymer‐coated removable stents were used to deliver 14 C‐labeled etretinate and 3 H‐labeled forskolin to the vessel wall in 31 New Zealand White rabbits to study their kinetics. Stents loaded with etretinate (n = 8) and forskolin (n = 14) were implanted in the rabbit carotid arteries, and the animals were euthanized at different time intervals. Drug levels were measured in the media and adventitia of the stented segment, in distant tissues, and in blood. In four rabbits, forskolin‐loaded stents were percutaneously retrieved 2 hr after implantation in the carotid artery, and the tissue and blood levels were determined 2 and 24 hr after retrieval. In seven rabbits etretinate‐loaded stents were retrieved 72 hr after implantation in abdominal aorta, and drug levels were measured in the tissues and blood immediately after and at 1 and 4 days after retrieval. Levels of etretinate in the vessel wall peaked at 24 hr (250 ng/mg) and remained high up to 72 hr (185 ng/mg) after stent placement. Levels of forskolin peaked within 2 hr of stent placement (135 ng/mg) and rapidly declined to 4.9 ng/mg at 24 hr with the stent in situ. About 50% (1.4 mg) of the original etretinate remained in the stent at 72 hr compared to about 5% (0.08 mg) of forskolin at 24 hr. Ratio of peak drug levels in the vessel wall to those in the blood was 6,000 for etretinate and 780 for forskolin. After stent removal at 72 hr, levels of etretinate in the aortic wall declined from 74 ng/mg to 29 ng/mg at 1 day and to 14 ng/mg at 4 days. Levels of forskolin declined rapidly within 2 hr of stent removal from 134 ng/mg to 1.2 ng/mg and further to 0.12 ng/mg within 24 hr. Polymer‐coated stents could be used for local drug delivery to the vessel wall. Kinetics of delivery and washout vary between drugs.