Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3-142H Katz Group Centre for Pharmacy and Health Research, Edmonton, AB, T6G 2E1, Canada.
Drugs R D. 2020 Dec;20(4):307-318. doi: 10.1007/s40268-020-00322-3.
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.
尼莫地平已被证明可改善蛛网膜下腔出血后的预后。指南建议所有患者接受 21 天的口服尼莫地平固定剂量治疗。然而，药代动力学研究表明，蛛网膜下腔出血和其他患者群体中尼莫地平的药代动力学存在变异性。这种变异性的临床相关性尚不清楚。因此，本综述的目的首先是进行文献回顾，总结不同患者群体中尼莫地平的药代动力学数据和变异性来源。其次，确定是否有证据表明蛛网膜下腔出血患者的尼莫地平暴露与临床结局之间存在关联。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"nymalize"或"nimotop")和("药代动力学*"或"PK")。检索结果仅限于英语和人类研究。已经报道了尼莫地平药代动力学的个体间变异性很大。影响药代动力学参数的患者特定因素包括年龄、合并症、遗传多态性和合并用药引起的代谢变异性，以及尼莫地平的给药技术。尼莫地平暴露与临床结局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，我们进行了系统的文献检索，提供了一篇叙述性综述，讨论了各种患者群体中尼莫地平的药代动力学变异性。尼莫地平系统暴露不足或缺乏是否会否认其益处，并导致蛛网膜下腔出血患者的结局恶化，目前尚不清楚。需要进一步的研究来确定是否存在这种关联。
