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原发性高血压患者口服替米沙坦和尼索地平单独及联合给药的药代动力学

Pharmacokinetics of oral doses of telmisartan and nisoldipine, given alone and in combination, in patients with essential hypertension.

作者信息

Bajcetic Milica, Benndorf Ralf A, Appel Daniel, Schwedhelm Edzard, Schulze Friedrich, Riekhof Daniel, Maas Renke, Böger Rainer H

机构信息

Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Unit, University Hospital Hamburg-Eppendorf, Martinistrasse 521, D-20246 Hamburg.

出版信息

J Clin Pharmacol. 2007 Mar;47(3):295-304. doi: 10.1177/0091270006297225.

Abstract

This randomized, single-blind, parallel-group study was performed to assess pharmacokinetic interactions potentially occurring during concomitant use of telmisartan and nisoldipine. Patients with essential hypertension (n = 37) were treated with once-daily doses of telmisartan, nisoldipine, or their combination for 6 weeks. The regimen was started at low dose with an increase of dosage after 3 weeks of treatment. AUC(ss) (132%; P < .01) of telmisartan applied in doses of 80 mg was significantly higher after concomitant application with nisoldipine (10 mg), whereas CL/f(ss) (-54%; P < .05) and Vz/f(ss) (-72%; P < .05) were significantly lower. Regarding pharmacokinetic parameters of nisoldipine, significant differences between treatment groups were not detected. In conclusion, the results of this study strongly suggest that concomitant treatment with nisoldipine enhances telmisartan bioavailability in hypertensive individuals. Larger crossover trials will have to establish these observations and investigate whether interaction of both drugs affects telmisartan efficacy and tolerability in clinical use.

摘要

本随机、单盲、平行组研究旨在评估替米沙坦与尼索地平联合使用时可能发生的药代动力学相互作用。37例原发性高血压患者接受每日一次剂量的替米沙坦、尼索地平或二者联合治疗,为期6周。治疗方案从低剂量开始,治疗3周后增加剂量。80mg剂量的替米沙坦与10mg尼索地平联合应用后,替米沙坦的AUC(ss)(132%;P < 0.01)显著升高,而CL/f(ss)(-54%;P < 0.05)和Vz/f(ss)(-72%;P < 0.05)显著降低。关于尼索地平的药代动力学参数,各治疗组之间未检测到显著差异。总之,本研究结果强烈提示,尼索地平联合治疗可提高高血压患者替米沙坦的生物利用度。更大规模的交叉试验将必须证实这些观察结果,并研究两种药物的相互作用是否会影响替米沙坦在临床应用中的疗效和耐受性。

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