title: Impact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing: A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis.
abstract: OBJECTIVE
  This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting.
  
  
  BACKGROUND
  The optimal therapeutic dose for PCB use has not been determined yet.
  
  
  METHODS
  Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment.
  
  
  RESULTS
  All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups.
  
  
  CONCLUSIONS
  Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gongora
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: Columbia University Medical Center, New York.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Wessler
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Jenn
authors.initials: J
authors.lastname: McGregor
authors.affiliation: Alizee Pathology, Thurmont, Maryland.
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Conditt
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.affiliation: Cardiovascular Research Foundation-Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, New York; Alizee Pathology, Thurmont, Maryland. Electronic address: jgranada@crf.org.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D057510:Endovascular Procedures / Q000009:adverse effects / Q000295:instrumentation*; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000150:complications*; D008670:Metals; D058426:Neointima; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D011859:Radiography; D015607:Stents; D013552:Swine; D014018:Tissue Distribution; D062666:Vascular Access Devices; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D008670:Metals; D005337:Fibrin; D017239:Paclitaxel
keywords: familial hypercholesterolemic swine; in-stent restenosis; paclitaxel-coated balloon