Abstract:
:Successful implementation of local arterial drug delivery requires transmural distribution of drug. The physicochemical properties of the applied compound, which govern its transport and tissue binding, become as important as the mode of delivery. Hydrophilic compounds distribute freely but are cleared rapidly. Hydrophobic drugs, insoluble in aqueous solutions, bind to fixed tissue elements, potentially prolonging tissue residence and biological effect. Paclitaxel is such a hydrophobic compound, with tremendous therapeutic potential against proliferative vascular disease. We hypothesized that the recent favorable preclinical data with this compound may derive in part from preferential tissue binding as a result of unique physicochemical properties. The arterial transport of paclitaxel was quantified through application ex vivo and measurement of the subsequent transmural distribution. Arterial paclitaxel deposition at equilibrium varied across the arterial wall and was everywhere greater in concentration than in the applied drug source. Permeation into the wall increased with time, from 15 minutes to 4 hours, and varied with the origin of delivery. In contrast to hydrophilic compounds, the concentration in tissue exceeds the applied concentration and the rate of transport was markedly slower. Furthermore, endovascular and perivascular paclitaxel application led to markedly differential deposition across the blood vessel wall. These data suggest that paclitaxel interacts with arterial tissue elements as it moves under the forces of diffusion and convection and can establish substantial partitioning and spatial gradients across the tissue. The complexity of paclitaxel pharmacokinetics requires in-depth investigation if this drug is to reach its full clinical potential in proliferative vascular diseases.
journal_name
Circ Resjournal_title
Circulation researchauthors
Creel CJ,Lovich MA,Edelman ERdoi
10.1161/01.res.86.8.879subject
Has Abstractpub_date
2000-04-28 00:00:00pages
879-84issue
8eissn
0009-7330issn
1524-4571journal_volume
86pub_type
杂志文章abstract::A narrow zone of block in isolated false tendon preparations was created by perfusion of the central compartment (gap) of a three-compartment tissue bath with either an isotonic sucrose solution or a solution designed to mimic the extracellular milieu in ischemic tissue. Driven responses on the proximal side of the ga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.5.1129
更新日期:1981-11-01 00:00:00
abstract::Spatial electrical heterogeneity has a profound effect on normal cardiac electrophysiology and genesis of cardiac arrhythmias in diseased hearts. The Na+-Ca2+ exchanger (NCX) is a key linker, through Ca2+ signaling, between contractility and arrhythmias. Here we characterize the differential transmural expression of N...
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pub_type: 杂志文章
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更新日期:2019-12-06 00:00:00
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pub_type: 杂志文章
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更新日期:2003-03-21 00:00:00
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更新日期:2004-04-16 00:00:00
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更新日期:2006-03-17 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.1.82
更新日期:1996-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.50.1.86
更新日期:1982-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1991-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:1977-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2011-02-04 00:00:00
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pub_type: 杂志文章
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更新日期:2003-08-08 00:00:00
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pub_type: 杂志文章
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更新日期:1987-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.5.736
更新日期:1985-05-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.772
更新日期:1976-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.2.379
更新日期:1993-08-01 00:00:00
abstract::Rationale: The overuse of antibiotics has been an important clinical issue, and antibiotic exposure is linked to alterations in gut microbiota, which has been related to risks of various chronic diseases such as cardiovascular disease and cancer. Also, duration of antibiotic exposure may be a risk factor of premature ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315279
更新日期:2020-01-31 00:00:00
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pub_type: 杂志文章
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更新日期:1983-05-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1997-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-07-09 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2018-04-13 00:00:00
abstract::In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.3.359
更新日期:1985-03-01 00:00:00
abstract::The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.5.702
更新日期:1984-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.3.600
更新日期:1981-09-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2013-11-08 00:00:00
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pub_type: 杂志文章
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更新日期:2002-05-17 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.222364
更新日期:2010-10-29 00:00:00