title: Fluorocopolymer-coated nitinol self-expanding paclitaxel-eluting stent: pharmacokinetics and vascular biology responses in a porcine iliofemoral model.
abstract: OBJECTIVE
  Our aim was to evaluate arterial responses to paclitaxel and a novel fluorocopolymer-coated nitinol low-dose paclitaxel-eluting stent (FP-PES).
  
  
  RESULTS
  Human smooth muscle cell (SMC) migration was assessed after exposure to paclitaxel in vitro. For pharmacokinetics and vascular response, FP-PES or bare metal stents (BMS) were implanted in porcine iliofemoral arteries. Paclitaxel significantly inhibited human coronary and femoral artery SMC migration at doses as low as 1 pM. Inhibition was significantly greater for femoral compared with coronary artery SMCs from 1 pM to 1 μM. Pharmacokinetics showed consistent paclitaxel release from FP-PES over the study duration. The peak arterial wall paclitaxel level was 3.7 ng/mg at 10 days, with levels decreasing to 50% of peak at 60 days and 10% at 180 days. Paclitaxel was not detected in blood or remote organs. Arteriogram and histomorphometry analyses showed FP-PES significantly inhibits neointimal proliferation versus BMS at 30 and 90 days. Re-endothelialisation scores were not different between groups.
  
  
  CONCLUSIONS
  Paclitaxel affected femoral artery SMC migration at lower concentrations and to a greater degree than it did coronary artery SMCs. The novel FP-PES used in this preclinical study demonstrated a vascular healing response similar to BMS, while significantly inhibiting neointimal formation up to 90 days.
authors.affiliation: Boston Scientific Corporation, Marlborough, MA, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Hou
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Huibregtse
authors.forename: Michael
authors.initials: M
authors.lastname: Eppihimer
authors.forename: William
authors.initials: W
authors.lastname: Stoffregen
authors.forename: Gordon
authors.initials: G
authors.lastname: Kocur
authors.forename: Cory
authors.initials: C
authors.lastname: Hitzman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stejskal
authors.forename: John
authors.initials: J
authors.lastname: Heil
authors.forename: Keith D
authors.initials: KD
authors.lastname: Dawkins
mesh_terms: D000497:Alloys; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002465:Cell Movement / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology; D054855:Drug-Eluting Stents; D005263:Femoral Artery / Q000166:cytology; D006801:Humans; D023421:Models, Animal; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D058426:Neointima / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers; D013552:Swine
chemical_list: D000497:Alloys; D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; C013616:nitinol; D017239:Paclitaxel