Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients
Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients
复制标题
DOI：
10.1177/147323000002800401
复制
发表时间：
2000-07-01
影响因子：
1.6
通讯作者：
Roth, W
中科院分区：
文献类型：
--
作者：
Stangier, J;Su, CAPF;Roth, W
在健康的年轻男性和健康的老年男性或女性中进行了一系列研究，以评估替米沙坦的药代动力学特征。此外，两项ii期临床试验评估了替米沙坦在轻中度高血压患者中的药代动力学和安全性。替米沙坦作为单次口服（1 - 160毫克）或静脉注射（10 - 160毫克）给年轻男性。在另一项多剂量研究中，健康年轻男性受试者口服替米沙坦320 mg，每天一次，持续7天。老年受试者口服替米沙坦（20和120 mg），每日1次，连用7天。替米沙坦剂量分别为10、20、40、80、120和160 mg，每日1次，连用7天。此外，对高血压患者口服替米沙坦（40,80或120mg），每天一次，持续28天。口服给药后，达到最大血浆替米沙坦浓度的中位时间为0.5 - 2小时，最大血浆浓度随剂量不成比例地增加。相比之下，血药浓度与静脉注射剂量直接相关。每日一次给药5 - 7天后观察到稳定状态，28天无临床相关积累。所有研究组的血药浓度-时间曲线相似，均表现为快速吸收和血药浓度峰值后快速双指数下降，终末消除期延长（健康和高血压受试者为bbb20 h）。替米沙坦耐受性良好，药物相关不良事件发生率低。最常见的事件是头痛，这也发生在安慰剂治疗的对照组中。接受替米沙坦后，心率、心电图和临床化学均未发生变化。因此，研究表明，在任何年龄的健康成人和高血压患者中，都可以达到耐受性良好的高全身水平的替米沙坦。较长的终末消除半衰期使替米沙坦适合每日一次给药，并有助于在整个24小时给药间隔内持续有效。
A series of studies was conducted in healthy young males and healthy elderly males or females to evaluate the pharmacokinetic profile of telmisartan. In addition, two phase-II clinical trials assessed the pharmacokinetics and the safety of telmisartan in mild-to-moderate hypertensive patients. Telmisartan was given as a single oral (1 - 160 mg) or intravenous (10 - 160 mg) dose to young males. In another multiple-dose study, telmisartan 320 mg was administered orally once daily for 7 days to healthy young male subjects. Elderly subjects received oral telmisartan (20 and 120 mg) once daily for 7 days. Telmisartan doses of 10, 20, 40, 80, 120 and 160 mg were taken once daily by mild-to-moderate hypertensive patients for 7 days. Additionally, oral telmisartan (40, 80 or 120 mg) was administered once daily for 28 days to hypertensive subjects. Following oral dosing, median time to maximum plasma telmisartan concentration was 0.5 - 2 h, with maximum plasma concentrations increasing disproportionately with dose. By contrast, plasma concentrations were directly related to the intravenous dose. Steady state was observed after 5 - 7 days of once-daily administration, and there was no clinically relevant accumulation at 28 days. The plasma concentration-time profiles were similar in all study groups and were characterized by fast absorption and a rapid biexponential decline after the peak plasma concentration, with a prolonged terminal elimination phase (> 20 h in healthy and hypertensive subjects). Telmisartan was well tolerated, with a low incidence of drug-related adverse events. The most frequent event was headache, which also occurred in placebo-treated control subjects. No changes in heart rate, electrocardiograms or clinical chemistry were detected following receipt of telmisartan, The study thus shows that high systemic levels of telmisartan, which are well tolerated, can be attained in healthy adults of any age and in hypertensive subjects. The long terminal elimination half-life makes telmisartan suitable for once-daily dosing and contributes to the sustained efficacy over the full 24-h dosing interval.