Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study.

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.