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Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug‐coated balloon in a swine femoral artery model
Author(s) -
Yazdani Saami K.,
Pacheco Erica,
Nakano Masataka,
Otsuka Fumiyuki,
Naisbitt Scott,
Kolodgie Frank D.,
Ladich Elena,
Rousselle Serge,
Virmani Renu
Publication year - 2013
Publication title -
catheterization and cardiovascular interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.988
H-Index - 116
eISSN - 1522-726X
pISSN - 1522-1946
DOI - 10.1002/ccd.24995
Subject(s) - medicine , paclitaxel , femoral artery , pharmacokinetics , balloon , artery , anesthesia , urology , surgery , chemotherapy
Objectives This study was designed to evaluate the safety of a novel drug‐coated balloon (DCB) with 2 µg/mm 2 paclitaxel and a carrier comprised of polysorbate and sorbitol in a swine femoral artery model. Background DCB have emerged as a therapeutic alternative in the treatment of peripheral vascular disease. Methods The femoral arteries of 45 swine were treated with low pressure balloon inflation either 1× clinical dose (single inflation, 2 µg/mm 2 paclitaxel) or 4× dose (2 DCBs, each with 4 µg/mm 2 paclitaxel) or control (uncoated) balloons. The treated arteries, downstream vascular beds, and organs were assessed histologically at 28, 90, and 180‐days. Twenty‐four swine were treated with 1× dose for pharmacokinetic analysis through 30 days. Results Arterial tissue paclitaxel concentration was 58.8 ± 54.2 ng/mg at 1‐hr and 0.3 ± 0.4 ng/mg at 30 days, whereas plasma paclitaxel could no longer be detected after 1 day. The treated arteries displayed minimal endothelial loss, fibrin deposition, and inflammation with long‐term dose‐dependent drug effect (medial smooth muscle cell loss) peaking at 90 days for both 1× (1.1 ± 1.4 vs. 0.0 ± 0.0, P = 0.008) and 4× dose (2.0 ± 1.5 vs. 0.0 ± 0.0, P < 0.001). In parallel, healing of the treated arteries was evident by significantly greater medial proteoglycan and collagen deposition at 180 days. No evidence of ischemia from downstream emboli or systemic toxicity was observed even for 4× DCB groups. Conclusions The findings indicate desired pharmacologic levels with biologic effects at early and healing at late time points in the treated arteries, without evidence of significant downstream emboli or systemic toxicity, consistent with safety of the Lutonix® DCB. © 2013 Wiley Periodicals, Inc.