Pharmacokinetics of propranolol after single and multiple dosing with sustained release propranolol or propranolol CR (innopran XL) , a new chronotherapeutic formulation.
Pharmacokinetics of propranolol after single and multiple dosing with sustained release propranolol or propranolol CR (innopran XL) , a new chronotherapeutic formulation.
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缓释普萘洛尔或普萘洛尔 CR（innopran XL）（一种新的时间治疗制剂）单次和多次给药后普萘洛尔的药代动力学。
DOI：
10.1097/01.hdx.0000074436.09658.3b
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
N. Manowitz
中科院分区：
文献类型：
--
作者：
D. Sica;W. Frishman;N. Manowitz
血压在清醒时迅速升高，可能是导致早晨心肌梗死和中风发病率增加的部分原因。目前的抗高血压药物的配方和剂量不能在这一脆弱时期提供最大的覆盖面。本研究旨在证明普萘洛尔CR（Innopran XL）（一种专为夜间给药设计的普萘洛尔新型计时制剂）具有适当的药代动力学，可在早晨提供最大的心脏保护作用。在这项开放标签、2阶段交叉研究中，在正常男性志愿者中测定了普萘洛尔CR和缓释普萘洛尔单次和多次给药后的药代动力学。药物在晚上给药，并在接下来的24至72小时内采集系列血液样品用于测定普萘洛尔浓度。在晚上10点单次给予160 mg普萘洛尔CR后，吸收延迟约4小时，之后血浆浓度稳步上升，在上午10点左右达到峰值。相反，在给予持续释放普萘洛尔后，普萘洛尔的血浆水平几乎立即开始上升，在上午4：00至上午10：00之间达到平台。在多次给药期间，任一药物均在2天后达到稳态血浆谷浓度。末次给药后，两种药物的血浆曲线与单次给药研究中观察到的相似。两种普萘洛尔制剂的生物利用度相似。普萘洛尔CR表现出适当的药代动力学慢性方法治疗高血压。
Blood pressure rises rapidly upon waking and may be responsible, in part, for the increased incidence of myocardial infarction and stroke during the morning hours. Current formulations and dosing of antihypertensive drugs do not provide maximum coverage during this vulnerable period. This study was performed to demonstrate that propranolol CR (Innopran XL), a novel chronotherapeutic formulation of propranolol designed for nighttime dosing, has appropriate pharmacokinetics to provide maximum cardioprotective effect in the morning. Pharmacokinetics of propranolol CR and sustained-release propranolol after single and multiple doses were determined in normal male volunteers in this open-label, 2-period crossover study. The drugs were dosed in the evening and serial blood samples were taken for determination of propranolol concentration the next 24 to 72 hours. After a single 160-mg dose of propranolol CR administered at 10 pm, absorption was delayed by about 4 hours, after which plasma concentration rose steadily, reaching a peak at about 10:00 am. In contrast, after dosing with sustained release propranolol, plasma levels of propranolol began to rise almost immediately, reaching a plateau between 4:00 am and 10:00 am. During multiple dosing, steady-state trough plasma concentrations were achieved after 2 days with either drug. After the final dose, the plasma profiles of both drugs were similar to those observed in the single-dose study. Bioavailability was similar for both formulations of propranolol. Propranolol CR exhibited appropriate pharmacokinetics for a chronotherapeutic approach to the treatment of hypertension.
影响因子：
37.8
作者：
RIDKER, PM;MANSON, JE;HENNEKENS, CH
通讯作者：
HENNEKENS, CH