E-ISSN: 1019-5157 ISSN: 2651-5024
Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study
Page : 148-159

AIM: To evaluate the effects of the combination of nimodipine and dexamethasone in subarachnoid hemorrhage (SAH).

MATERIAL and METHODS: In this study, 35 female adult Wistar Albino rats were randomly assigned to four groups: Sham (n=8), SAH with no treatment (n=9), SAH with nimodipine (n=9, oral gavage, 12 mg/kg, BID) treatment, and SAH with combined therapy with nimodipine and dexamethasone (n=9, intraperitoneally, 1mg/kg, BID). The ?cisterna magna double injection of autologous blood? model was used. The animals were euthanized 5 days after the first injection.

RESULTS: Of the total, five rats died before euthanasia. The SAH+Nontreatment group showed the worst score in neurological examinations, and the most severe histopathological findings were noted in terms of vasospasm. The SAH+Nimodipine group showed the best neurological score and the closest histopathological results to those of the Sham group, whereas adding dexamethasone to nimodipine treatment (the SAH+Nimodipine+Dexamethasone group) worsened the neurological and histopathological outcomes.

CONCLUSION: We thus concluded that the therapeutic effects of nimodipine were impaired when combined with dexamethasone. We thus hypothesized that dexamethasone possibly induces the CYP3A4-enzyme that metabolizes nimodipine. However, it should be noted that our results are based on laboratory findings obtained on a small sample, therefore further studies with drug?drug interaction on a larger sample size through CYP3A4-enzyme and clinical confirmation are warranted.

Keywords : Delayed Cerebral Ischemia Dexamethasone Nimodipine Subarachnoid Hemorrhage Vasospasm
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