Cerebral Ischemia Protection After Aneurysmal Subarachnoid Hemorrhage: CSF Nimodipine Levels After Intravenous Versus Oral Nimodipine Administration.

Autor: Moser MM; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Rössler K; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Hirschmann D; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Gramss L; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Tahir A; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Plöchl W; Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Division of General Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria., Herta J; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Reinprecht A; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria., Zeitlinger M; Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria., Hosmann A; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Nov 19. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1002/cpt.3499
Abstrakt: There is accumulating evidence that cerebrospinal fluid (CSF) concentrations of nimodipine correlate with long-term outcome of patients after subarachnoidal hemorrhage (aSAH) by impeding cerebral ischemia. However, pharmacological data on simultaneous serum vs. CSF and intraparenchymal nimodipine values are rarely reported in larger patient groups. Nimodipine concentrations were determined in plasma, CSF, and cerebral interstitial fluid (ISF), at steady state after oral (6 × 60 mg/day) and intravenous (0.5, 1, 1.5 and 2 mg/h) administrations in 10 patients after aSAH. Area under the concentration time curve (AUC 0-24 ) for intravenous nimodipine was highest at an infusion rate of 2 mg/h in plasma (1335.87 ± 591.09 mg*h/L), followed by CSF (39.53 ± 23.07 mg*h/L), resulting in an overall CSF penetration ratio of 3.8% (±1.5) (AUC CSF /AUC plasma ). In contrast, nimodipine levels were significantly lower in both plasma (AUC 0-24 298.32 ± 206.52 mg*h/L) and CSF (AUC 0-24 34.8 ± 16.56 mg*h/L) after oral administration. In cerebral ISF, low amounts of nimodipine were detectable in only 4 patients at an infusion rate of 1.5 and 2 mg/h as well as following oral administration. We found significantly higher CSF nimodipine levels in patients during intravenous compared to oral administration. In contrast, only low amounts of nimodipine were detected in the ISF after both oral and intravenous administration. Our findings strongly suggest that the main clinical nimodipine effect of impeding life threatening cerebral ischemia is mediated through significant higher CSF levels after intravenous administration, more likely effective than oral administration.
(© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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