Taxane in Contrast Medium Inhibits Restenosis

The results of their work were presented at the annual congress of the European Society of Cardiology (ESC) in Berlin (Germany).

X-ray contrast media are necessary to visualize the coronary arteries for diagnostic and therapeutic procedures. These contrast agents occasionally delineate the contour of coronary arteries for some seconds after the initial washout. The researchers speculated that such a layer of contrast agent remaining adjacent to the endothelium where the flow velocity is very low might possibly act as a matrix for antiproliferative drugs to prevent stenosis. Antiproliferative drugs seemed suitable because of their high lipophilicity and tight binding to cell constituents, resulting in local retention at the delivery site. This approach does not require a particular delivery device or a special stent. Early experiments indicated that cells incubated for only three minutes with the contrast medium incorporating taxane were prevented from proliferation for up to two weeks.

The researchers then tested the efficacy of different formulations of paclitaxel added to the contrast agent iopromide in a porcine stent model. They implanted 34 stents into the coronary arteries of 17 pigs, comparing four groups: conventional contrast agent, intravenous iopromide plus 12.8 mg of paclitaxel, intracoronary iopromide plus 6.4 mg paclitaxel, and intracoronary iopromide with 12.8 mg of paclitaxel. Quantitative coronary analysis showed there was a marked reduction of all parameters relevant to in-stent restenosis in favor of the intracoronary iopromide-paclitaxel.

The researchers, from the University of Saarland (Homburg, Germany), say the study also shows that the novel drug delivery mechanism is efficient at subtoxic systemic levels of the cytostatic agent. Thus, contrast media as drug carriers may be an alternative to expensive drug-coated stents.





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Univ. of Saarland