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 rapamyci...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 (C_ max), time to peak concentration (t_ max), elimination half-life (t_ 1/2β), 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·h·ml -1, and (180±12) ml·h -1·kg -1, respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart.Conclusion Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.展开更多
文摘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 (C_ max), time to peak concentration (t_ max), elimination half-life (t_ 1/2β), 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·h·ml -1, and (180±12) ml·h -1·kg -1, respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart.Conclusion Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.
