Stent elution rate determines drug deposition and receptor-mediated effects.
Stent elution rate determines drug deposition and receptor-mediated effects.
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DOI：
10.1016/j.jconrel.2012.05.039
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发表时间：
2012-08-10
期刊：
影响因子：
--
通讯作者：
Edelman ER
中科院分区：
文献类型：
--
作者：
Tzafriri AR;Groothuis A;Price GS;Edelman ER
药物洗脱支架设计很多，但疗效对药物剂量和洗脱持续时间的依赖性仍不清楚。我们在支架洗脱后动脉药物分布和受体结合的数学框架内研究了这些问题。在猪冠状动脉西罗莫司洗脱支架植入物中验证了组织含量线性跟踪支架洗脱速率的模型预测。动脉内容物因支架类型而异，从第1天峰值逐渐下降，并跟踪限速药物洗脱-接近零级释放在支架病变中沉积药物的效率是接近一级释放的三倍。体内数据与相对于特异性受体和递送剂量的非特异性西罗莫司结合位点过多一致。这意味着受体饱和和效应的持续时间对洗脱时间比洗脱量更敏感。因此，洗脱量应足够高以使靶病变处的受体饱和，但单独的剂量递增是延长西罗莫司沉积持续时间的无效策略。此外，当以恒定零级方式从支架洗脱时，预计受体饱和药物剂量最有效，因为这使洗脱和受体饱和的持续时间最大化。
Drug eluting stent designs abound and yet the dependence of efficacy on drug dose and elution duration remains unclear. We examined these issues within a mathematical framework of arterial drug distribution and receptor binding following stent elution. Model predictions that tissue content linearly tracks stent elution rate were validated in porcine coronary artery sirolimus-eluting stents implants. Arterial content varied for stent types, progressively declining from its Day 1 peak and tracking with rate-limiting drug elution – near zero-order release was three-fold more efficient at depositing drug in the stented lesion than near first-order release. In vivo data were consistent with an overabundance of non-specific sirolimus-binding sites relative to the specific receptors and to the delivered dose. The implication is that the persistence time of receptor saturation and effect is more sensitive to duration of elution than to eluted amount. Consequently, the eluted amount should be sufficiently high to saturate receptors at the target lesion, but dose escalation alone is an inefficient strategy for prolonging the duration of sirolimus deposition. Moreover, receptor saturating drug doses are predicted to be most efficacious when eluted from stents in a constant zero order fashion as this maximizes the duration of elution and receptor saturation.
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影响因子：
10.8
作者：
Balakrishnan, Brinda;Dooley, John;Kopia, Gregory;Edelman, Elazer R.
通讯作者：
Edelman, Elazer R.
影响因子：
4.9
作者：
Hossainy, Syed;Prabhu, Santosh
通讯作者：
Prabhu, Santosh
影响因子：
4.9
作者：
Balss, K. M.;LIanos, G.;Maryanoff, C. A.
通讯作者：
Maryanoff, C. A.
影响因子：
37.8
作者：
Hausleiter, J;Kastrati, A;Schömig, A
通讯作者：
Schömig, A
DOI：
10.1073/pnas.87.23.9231
发表时间：
1990-12-01
影响因子：
11.1
作者：
BIERER, BE;MATTILA, PS;SCHREIBER, SL
通讯作者：
SCHREIBER, SL