Nimodipine Pharmacokinetic Variability in Various Patient Populations
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REVIEW ARTICLE
Nimodipine Pharmacokinetic Variability in Various Patient Populations Sherif Hanafy Mahmoud1 · Xinqi Ji1 · Fadumo Ahmed Isse1
© The Author(s) 2020
Abstract 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.
Key Points
1 Introduction
Nimodipine exposure is highly variable among individuals.
Nimodipine is a dihydropyridine calcium channel blocker with greater selectivity for cerebral blood vessels than other agents within the same class [1, 2]. As a result, nimodipine has been tested in the setting of aneurysmal subarachnoid hemorrhage (SAH), a life-threatening brain bleed. Neurological and medical complications are common following SAH and contribute significantly to the overall prognosis. Cerebral vasospasm and delayed cerebral ischemia (DCI) are examples of those complications and are considered as significant contributors of disability in patients with SAH who survive the initial bleed [3, 4]. Effective prevention of DCI can significantly improve the functional outcomes of patients. Therefore, a substantial amount of research in this area has been focused on understanding the mechanisms of those complications and exploring potential therapeutic modalities for improving patient outcomes. Several agents have been investigate
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