Pharmacokinetics of rapamycin-eluting stents in miniswine coronary model.
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.
Yu
Meng-yue
MY
Cardiovascular Institute, Fuwai Hospital, China.
Gao
Run-lin
RL
Jiang
Ji
J
Cheng
Shu-jun
SJ
Yuan
Jin-qing
JQ
Wang
Chun-ning
CN
Zheng
Jin-gang
JG
Meng
Liang
L
Zi
Zhen-jun
ZJ
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
D020123:Sirolimus