Prophylactic intravenous nimodipine treatment in skull base surgery: pharmacokinetic aspects.

University of Halle-Wittenberg, Department of Neurosurgery, Halle (Saale), Germany.
Journal of neurological surgery. Part A, Central European neurosurgery 01/2012; 73(3):153-9. DOI: 10.1055/s-0032-1313724
Source: PubMed

ABSTRACT Nimodipine is primarily used in subarachnoid hemorrhage (SAH). Clinical trials revealed also a beneficial effect of prophylactic nimodipine treatment on cranial nerve functions following vestibular schwannoma surgery.
The unknown pharmacokinetics of prophylactically administered nimodipine were investigated.
Samples were taken from 27 patients with skull base lesions. Prophylactic intravenous nimodipine infusion was started 5.8-25.8 h (mean 17.9 h) before surgery. Nimodipine concentrations were determined in serum (intra- and postoperatively), cerebrospinal fluid (CSF) (intraoperatively), and tissue samples.
Wide interindividual differences were observed. Mean concentrations for nimodipine were 46.9 ng/ml (SD: 6.4; min. 4.1 and max. 92.7 ng/ml) in intraoperative serum, 73.2 ng/ml (SD: 16.7; min. 6.6 and max. 253 ng/ml) in postoperative serum and 8.3 ng/ml (SD: 1.5; min. 1.0 und max. 29.7 ng/ml) in intraoperative CSF. The correlation between intra- and postoperative serum (p=0.004, r=0.560) and between intra-operative serum and CSF concentration (p=0.003, r=0.567) were statistically significant. Furthermore the correlation between intraoperative serum concentration and concentrations collected from vestibular nerves was high (r=0.711), but not statistically significant (p=0.178).
Interindividually, continously administered intravenous nimodipine produces considerably variable serum levels. Controls of nimodipine serum concentrations may be useful to optimize nimodipine medication in skull base surgery and in the management of SAH. The serum nimodipine level is a useful marker for CSF and intracranial nerve tissue concentrations of nimodipine.

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    ABSTRACT: Nimodipine is well characterized for the management of SAH (subarachnoid hemorrhage) and has been shown to promote a better outcome and less DIND (delayed ischemic neurological deficits). In rat experiments, enhanced axonal sprouting and higher survival of motoneurons was demonstrated after cutting or crushing the facial nerve by nimodipine. These results were confirmed in clinical trials following vestibular Schwannoma surgery. The mechanism of the protective competence of nimodipine is unknown. Therefore, in this study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. Our findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine.
    International Journal of Molecular Sciences 10/2014; 15(10):18453-18465. · 2.34 Impact Factor


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May 16, 2014