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阿替洛尔在慢性肝病患者中的临床经验。

Clinical experience with atenolol in patients with chronic liver disease.

作者信息

Kirch W, Schäfer-Korting M, Mutschler E, Ohnhaus E E, Braun W

出版信息

J Clin Pharmacol. 1983 Apr;23(4):171-7. doi: 10.1002/j.1552-4604.1983.tb02721.x.

Abstract

The pharmacokinetics of atenolol were investigated following single intravenous (25 mg) and oral administration (100 mg) of atenolol in 13 patients with chronic liver disease and normal renal function and in 12 normal healthy volunteers. Four of the patients with chronic liver disease were not included in the statistical evaluation of kinetic data, since a reduction of creatinine clearance was observed during the course the study after ingestion of atenolol. A tendency to an increased distribution volume of atenolol could be observed in subjects with liver disease compared to normal volunteers. After intravenous and oral administration of atenolol, pharmacokinetic parameters such as elimination half-life, plasma clearance, and renal clearance did not differ significantly between patients with chronic liver disease and healthy volunteers. Thus, plasma half-life after intravenous dosing of atenolol was 6.0 +/- 0.46 hours in patients with hepatic disease and 5.0 +/- 0.4 hours in the controls, indicating absence of atenolol accumulation in hepatic failure. In the first days after starting beta-blocker therapy such as atenolol administration, parameters of kidney function as plasma creatinine, or possibly creatinine clearance, should be initially monitored at regular intervals, as there may be transient changes of renal function in patients with chronic liver disease, leading to delayed elimination of the drug.

摘要

在13例慢性肝病且肾功能正常的患者以及12名正常健康志愿者中,分别单次静脉注射(25毫克)和口服(100毫克)阿替洛尔后,对其药代动力学进行了研究。有4例慢性肝病患者未纳入动力学数据的统计评估,因为在服用阿替洛尔后的研究过程中观察到肌酐清除率降低。与正常志愿者相比,在肝病患者中可观察到阿替洛尔分布容积有增加的趋势。静脉注射和口服阿替洛尔后,慢性肝病患者和健康志愿者之间的药代动力学参数如消除半衰期、血浆清除率和肾清除率没有显著差异。因此,肝病患者静脉注射阿替洛尔后的血浆半衰期为6.0±0.46小时,对照组为5.0±0.4小时,表明肝衰竭时阿替洛尔无蓄积。在开始β受体阻滞剂治疗(如服用阿替洛尔)后的最初几天,应定期监测肾功能参数如血浆肌酐或可能的肌酐清除率,因为慢性肝病患者的肾功能可能会有短暂变化,导致药物消除延迟。

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