Paclitaxel-induced arterial wall toxicity and inflammation: tissue uptake in various dose densities in a minipig model

Journal of Vascular and Interventional Radiology : JVIR
Boris RadeleffGoetz M Richter

Abstract

Paclitaxel is an antiproliferative agent in drug-eluting stents with largely unknown tissue interaction. Toxicity might result from overdosage and/or accumulation. Part 1 of this two-step study investigated how paclitaxel uptake depends on dose density, coronary drug transfer kinetics, and elution efficacy. With cobalt chromium stents and Polyzene-F nanoscale coating, low, intermediate, and high paclitaxel dose densities (25 microg, 50 microg, and 150 microg per stent) were investigated in porcine right coronary arteries (RCAs). Coronary and myocardial tissue concentration measurements and determination of on-stent paclitaxel and plasma concentrations were performed at 2, 8, 24, and 72 hours. For all stents, uptake was similar at all time intervals (paclitaxel RCA concentration range, 1,610-33,300 ng). Low- and intermediate-dose stents showed similar RCA concentrations, but those for high-dose stents were three times greater. Residual on-stent paclitaxel concentration was not time-dependent, at 33.3% on low-, 30.6% on intermediate-, and 17.4% on high-dose stents. Paclitaxel was measurable in only the plasma immediately after stent placement, with a linear dose relationship and a timely regression: measurements in high-dose sten...Continue Reading

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Citations

Jan 8, 2014·Biomechanics and Modeling in Mechanobiology·Franz BozsakAbdul I Barakat
Jul 21, 2015·Journal of Vascular and Interventional Radiology : JVIR·Rocío Fernández-ParraMiguel A de Gregorio
Jun 18, 2015·PloS One·Franz BozsakAbdul I Barakat
Sep 6, 2018·Scandinavian Journal of Surgery : SJS : Official Organ for the Finnish Surgical Society and the Scandinavian Surgical Society·P BjörkmanM Venermo
Dec 7, 2018·Frontiers in Pharmacology·Hannah A StrobelMarsha W Rolle

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