Nimodipine Pharmacokinetic Variability in Various Patient Populations

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 Nimodipine exposure is highly variable among individuals. Age, liver disease, genetic make-up, and nimodipine administration techniques influence nimodipine exposure.

Relativistic reflection in NGC 4151

“…In our best spectral model the truncation occurs relatively close to the black hole (within a 100R g ) when the source is bright in hard X-rays, and reflec-tion from the inner disk is weak, R disk ∼ 0.2, which implies that the vertical scale height of the flow is small. Our best model is consistent with the spectral-timing model proposed for NGC 4151 by Mahmoud & Done (2020), where the main reprocessing of the X-ray radiation occurs in optically thin clouds on size scales of the BLR. The presence of the inner disk estimated in our analysis does not conflict with the dominating reprocessing in the BLR, because only a small fraction of X-rays is reprocessed in the disk.…”

Nimodipine Treatment Protects Auditory Hair Cells from Cisplatin-Induced Cell Death Accompanied by Upregulation of LMO4

“…In parallel, in vitro studies on neuronal and Schwann cells showed a lower cytotoxic effect after nimodipine pre-treatment under different stress conditions [ 6 , 36 ]. The use of nimodipine has been established over the last 40 years, and its good tolerability, already proven in vivo, suggests that in addition to the standard treatment of vasospasm following subarachnoid hemorrhage, the use of nimodipine in clinical practice can be further extended [ 1 , 2 , 3 ]. In this study, the effect of nimodipine on cisplatin-induced apoptosis of inner ear hair cells was investigated for the first time.…”

“…Nimodipine belongs to the group of 1,4-dihydropyridines and exerts its effects by binding to the alpha1 subunit of L-type calcium channels, thereby decreasing calcium influx via negative allosteric inhibition [ 1 , 2 ]. Although nimodipine is one of the first calcium channel antagonists to be developed, it has been the focus of medical and scientific attention again [ 1 , 3 , 4 , 5 , 6 ]. Due to its good cerebrospinal fluid penetrability [ 2 ], which distinguishes it from other calcium antagonists of its substance class, nimodipine acts in the central nervous system.…”

“…Due to its good cerebrospinal fluid penetrability [ 2 ], which distinguishes it from other calcium antagonists of its substance class, nimodipine acts in the central nervous system. Because of this, nimodipine is routinely used in the clinic for the prophylaxis of cerebral vasospasm after subarachnoid hemorrhage by relaxing the smooth muscle of cerebral blood vessels, causing vasodilatation [ 1 , 3 ]. Nimodipine has also been administered in the area of ischemic stroke, traumatic brain injury, and migraine to investigate whether treatment leads to a positive outcome, but with heterogeneous results [ 1 ].…”

A Review of Genetic Polymorphisms and Susceptibilities to Complications after Aneurysmal Subarachnoid Hemorrhage

“…However, not all patients respond to this drug successfully. This variability may be due to different factors such as age, sex, comorbidities, and metabolic variations due to individual genetic susceptibility which is determined, among other factors, by the presence of polymorphic genetic variants [ 17 ].…”