title: Pharmacokinetic Study of Paclitaxel Concentration after Drug-Eluting Balloon Angioplasty in the Iliac Artery of Healthy and Atherosclerotic Rabbit Models.
abstract: OBJECTIVE
  To assess whether the presence of an atherosclerotic lesion may alter the deposition kinetics of paclitaxel on the arterial wall after drug-eluting balloon (DEB) angioplasty, as well as paclitaxel concentrations in serum and in the recovered balloons.
  
  
  METHODS
  Three New Zealand White rabbit models were created: an atheroma group (arterial mechanical injury and hyperlipidic diet; group A), a prelesional group (fat arterial infiltration, hyperlipidic diet; group B), and a control healthy group (group C). Forty-five animals underwent DEB angioplasty in the iliac artery. Arteries and serum samples were analyzed by liquid chromatography/tandem mass spectrometry at 1, 24, 48, 72, and 96 hours (arteries) and at 1, 6, 12, and 24 hours (serum). Recovered balloons were analyzed by UV chromatography. Histologic and statistical analyses were also performed.
  
  
  RESULTS
  Group A showed significantly higher arterial paclitaxel concentrations in the first hour after DEB angioplasty (632.05 ng/mg ± 125.75 in group A vs 179.55 ng/mg ± 45.64 and 168.54 ng/mg ± 83.48 in groups B and C, respectively; P < .05). Paclitaxel was undetectable in serum at 24 hours in all groups, but the amount was significantly higher (P < .05) in group B at 1, 6, and 12 hours. The paclitaxel amount in navigated balloons from group A was significantly lower than in other groups (P < .05).
  
  
  CONCLUSIONS
  Paclitaxel concentration in an atherosclerotic lesion model immediately after DEB angioplasty is nearly fourfold higher than in a healthy artery. Paclitaxel remains in the bloodstream longer when a universal state of fat arterial infiltration is achieved. These findings could have clinical implications, as studies testing commercial drug-eluting devices on healthy animals may be underestimating paclitaxel arterial uptake.
authors.affiliation: Department of Animal Pathology, Universidad de Zaragoza, Zaragoza, Spain; Group Interventional Technics Minimal Invasive (GITMI), Zaragoza, Spain. Electronic address: rocio.f.parra@gmail.com.
authors.forename: Rocío
authors.initials: R
authors.lastname: Fernández-Parra
authors.affiliation: Department of Animal Pathology, Universidad de Zaragoza, Zaragoza, Spain; Group Interventional Technics Minimal Invasive (GITMI), Zaragoza, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Laborda
authors.affiliation: Group Interventional Technics Minimal Invasive (GITMI), Zaragoza, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Lahuerta
authors.affiliation: Faculty of Veterinary Sciences, Universidad de Zaragoza, Zaragoza, Spain; Group Interventional Technics Minimal Invasive (GITMI), Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lostalé
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Sciences, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Aramayona
authors.affiliation: Department of Animal Pathology, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: de Blas
authors.affiliation: Faculty of Veterinary Sciences, Universidad de Zaragoza, Zaragoza, Spain; Group Interventional Technics Minimal Invasive (GITMI), Zaragoza, Spain; CIBER-BBN I3A, Zaragoza, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: de Gregorio
mesh_terms: D000800:Angioplasty, Balloon / Q000379:methods*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D054855:Drug-Eluting Stents; D007083:Iliac Artery / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008657:Metabolic Clearance Rate; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D050257:Tubulin Modulators; D017239:Paclitaxel