title: Arterial pharmacokinetics of red wine polyphenols: implications for novel endovascular therapies targeting restenosis.
abstract: Drug-eluting stents (DESs) are endovascular devices that provide controlled release of compounds to interfere with restenosis, an adverse outcome of angioplasty characterized by thickening of the arterial wall. Accumulating evidence suggests that arterial pharmacokinetics determine the biological effect and potential toxicity of stent-based therapeutics. The aim of this study was to examine how drug polarity, drug load, and protein binding influence release from a polymer film and distribution within arterial tissue. The transport and safety profile of resveratrol (RESV) and quercetin (QUER), two red wine polyphenols known to interfere with events in the pathogenesis of restenosis, were compared with paclitaxel (Taxol), a lipophilic drug used in DES. In bovine arteries, RESV showed considerable protein binding and arterial kinetics that were found to mimick Taxol. In contrast, the less lipophilic QUER showed limited tissue distribution. Measured diffusivity of RESV and QUER was coupled with a novel computational method for assessment of biphasic drug release kinetics and arterial drug retention profiles. Modeling revealed that drugs associated with high- and low-protein-binding affinity result in markedly distinct arterial drug profiles. These data underscore the importance of arterial partitioning and propagation of drug within arterial tissue in the rational design of DES coatings.
authors.affiliation: Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kleinedler
authors.forename: Ilija
authors.initials: I
authors.lastname: Pjescic
authors.forename: Kirby K
authors.initials: KK
authors.lastname: Bullock
authors.forename: Abdul
authors.initials: A
authors.lastname: Khaliq
authors.forename: John D
authors.initials: JD
authors.lastname: Foley
authors.forename: Tammy R
authors.initials: TR
authors.lastname: Dugas
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002417:Cattle; D006083:Graft Occlusion, Vascular / Q000378:metabolism*; D017239:Paclitaxel / Q000493:pharmacokinetics; D059808:Polyphenols / Q000493:pharmacokinetics*; D014920:Wine / Q000032:analysis*
chemical_list: D059808:Polyphenols; D017239:Paclitaxel