title: Pharmacokinetics of rapamycin-eluting stents in miniswine coronary model.
abstract: BACKGROUND
  The results of clinical trials of rapamycin-eluting stents reduce restenosis have been quite promising. The main purpose of this study was to characterize the in vivo pharmacokinetics of high dose rapamycin (Rapa)-eluting stents in a miniswine coronary model.
  
  
  METHODS
  Ten miniswines underwent placement of 18 high dose Rapa-eluting stents in the left anterior descending and right coronary arteries. At the planned times of the 1.5th, 12th, 24th hour, 3th, 7th and 28th day, the animals (n = 1, 1, 2, 2, 2, and 2, respectively) were euthanized after completion of coronary angiography. Blood samples were obtained at 0, 10, 20, 30 minutes; 1, 2, 6, 24 hours; and 3, 7, 28 days to determine systemic Rapa levels. Rapa levels in whole blood, arterial wall, heart, renal and liver tissues were determined by high-performance liquid chromatography/mass spectroscopy.
  
  
  RESULTS
  Peak whole blood concentration (Cmax), time to peak concentration (tmax), elimination half-life (t1/2beta), area under the curve (AUC), and apparent systemic clearance (Cl/F) were (10.91 +/- 1.28) ng/ml, (2.0 +/- 0.2) hours, (7.25 +/- 0.63) hours, (1.15 +/- 0.11) ng x h x ml(-1), and (180 +/- 12) ml x h(-1) x kg(-1), respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart.
  
  
  CONCLUSIONS
  Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.
authors.affiliation: Cardiovascular Institute, Fuwai Hospital, China.
authors.forename: Meng-yue
authors.initials: MY
authors.lastname: Yu
authors.forename: Run-lin
authors.initials: RL
authors.lastname: Gao
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Shu-jun
authors.initials: SJ
authors.lastname: Cheng
authors.forename: Jin-qing
authors.initials: JQ
authors.lastname: Yuan
authors.forename: Chun-ning
authors.initials: CN
authors.lastname: Wang
authors.forename: Jin-gang
authors.initials: JG
authors.lastname: Zheng
authors.forename: Liang
authors.initials: L
authors.lastname: Meng
authors.forename: Zhen-jun
authors.initials: ZJ
authors.lastname: Zi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D023903:Coronary Restenosis / Q000517:prevention & control*; D008297:Male; D013058:Mass Spectrometry; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution
chemical_list: D020123:Sirolimus