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尼莫地平在肾功能正常和受损患者中的临床药代动力学

Clinical pharmacokinetics of nimodipine in normal and impaired renal function.

作者信息

Kirch W, Rämsch K D, Dührsen U, Ohnhaus E E

出版信息

Int J Clin Pharmacol Res. 1984;4(5):381-4.

PMID:6519852
Abstract

Twelve patients with different degrees of renal function were investigated. Six of them had moderately impaired renal function (glomerular filtration rate-GFR 20-60 ml/min) and six were preuraemic (GFR less than 20 ml/min). Patients received a single oral dose of 30 mg nimodipine on the first and eighth day, from the second to the seventh day they received 30 mg thrice daily. The results of this study were compared with the data of a similar study with six healthy volunteers (GFR greater than 90 ml/min) who also received for one week nimodipine 40 mg three times daily. In these subjects peak plasma levels of nimodipine ranged between 15.5 and 106.7 micrograms/1 on first treatment day and did not differ significantly from those on the 7th day of therapy ranging between 17.0 and 80 micrograms/1. Mean terminal elimination half-life of nimodipine was 2.77 +/- 0.46 h in normal renal function, but was 22.23 +/- 6.94 h in patients with impaired renal function (12 patients with GFR less than 60 ml/min). The mean area under the plasma level time curve (AUC) with 541.5 +/- 16.93 ng ml-1 h increased in patients with renal insufficiency compared to those with normal renal function (74.65 +/- 9.44 ng ml-1 h). Dosage adjustment of nimodipine appears to be necessary in renal failure.

摘要

对12例肾功能程度不同的患者进行了研究。其中6例肾功能中度受损(肾小球滤过率-GFR为20-60毫升/分钟),6例处于尿毒症前期(GFR低于20毫升/分钟)。患者在第一天和第八天口服单次剂量30毫克尼莫地平,从第二天到第七天每天三次服用30毫克。本研究结果与另一项类似研究的数据进行了比较,该研究对6名健康志愿者(GFR大于90毫升/分钟)进行了为期一周的每日三次、每次40毫克尼莫地平的给药。在这些受试者中,尼莫地平在首次治疗日的血浆峰值水平在15.5至106.7微克/升之间,与治疗第7天(水平在17.0至80微克/升之间)相比无显著差异。在肾功能正常的情况下,尼莫地平的平均终末消除半衰期为2.77±0.46小时,但在肾功能受损的患者(12例GFR低于60毫升/分钟的患者)中为22.23±6.94小时。与肾功能正常的患者(74.65±9.44纳克·毫升-1·小时)相比,肾功能不全患者的血浆水平时间曲线下平均面积(AUC)为541.5±16.93纳克·毫升-1·小时,有所增加。在肾衰竭患者中似乎有必要调整尼莫地平的剂量。

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