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Nimodipine Pharmacokinetic Variability in Various Patient Populations.
Drugs in R&D ( IF 2.2 ) Pub Date : 2020-09-09 , DOI: 10.1007/s40268-020-00322-3
Sherif Hanafy Mahmoud 1 , Xinqi Ji 1 , Fadumo Ahmed Isse 1
Affiliation  

Nimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral nimodipine for 21 days. However, pharmacokinetic studies have suggested variability of nimodipine pharmacokinetics in subarachnoid hemorrhage and in other patient populations. The clinical relevance of such variability is unknown. Therefore, the objective of the present review is, first, to conduct a literature review and summarize nimodipine pharmacokinetic data and sources of variability in various patient groups. Second, to determine if there is any evidence reporting an association between nimodipine exposure and clinical outcomes in patients with subarachnoid hemorrhage. A systematic literature search was performed in MEDLINE and EMBASE. The following keywords were used: (“nimodipine” OR “nymalize” OR “nimotop”) AND (“pharmacokinetic*”, OR “PK”). The search results were limited to English language and human studies. A large interpatient variability in nimodipine pharmacokinetics has been reported. Patient-specific factors that had an influence on pharmacokinetic parameters are age, comorbidities, variabilities in metabolism due to genetic polymorphism and co-administered medications, as well as nimodipine administration technique. The association between nimodipine exposure and clinical outcomes remains unclear and data available are too scarce to reach a firm conclusion. Here, we present a narrative review with a systematic literature search discussing nimodipine pharmacokinetic variability in various patient populations. It is not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening outcomes in patients with subarachnoid hemorrhage. Further studies are needed to determine if such an association exists.



中文翻译:

尼莫地平在不同患者人群中的药代动力学变异性。

尼莫地平已被证明可以改善动脉瘤性蛛网膜下腔出血后的预后。指南建议所有患者接受固定剂量的口服尼莫地平 21 天。然而,药代动力学研究表明,在蛛网膜下腔出血和其他患者人群中,尼莫地平的药代动力学存在差异。这种变异性的临床相关性是未知的。因此,本综述的目的首先是进行文献综述并总结尼莫地平药代动力学数据和不同患者组变异的来源。其次,确定是否有任何证据报告尼莫地平暴露与蛛网膜下腔出血患者的临床结果之间存在关联。在 MEDLINE 和 EMBASE 中进行了系统的文献检索。使用了以下关键字:(“尼莫地平”或“尼莫地平”或“尼莫托普”)和(“药代动力学*”,或“PK”)。搜索结果仅限于英语语言和人类研究。据报道,尼莫地平的药代动力学在患者之间存在很大差异。影响药代动力学参数的患者特异性因素包括年龄、合并症、由于遗传多态性和联合用药引起的代谢变化,以及尼莫地平给药技术。尼莫地平暴露与临床结果之间的关联仍不清楚,可用数据太少,无法得出明确的结论。在这里,我们通过系统性文献检索进行叙述性综述,讨论尼莫地平在不同患者人群中的药代动力学变异性。尚不清楚尼莫地平全身暴露很少或缺乏是否会否定其益处并导致蛛网膜下腔出血患者预后恶化。需要进一步的研究来确定这种关联是否存在。

更新日期:2020-09-10
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