Serum levels of nimodipine in enteral and parenteral administration in patients with aneurysmal subarachnoid hemorrhage

BACKGROUND: The aim of this study was to evaluate serum nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage (SAH) after parenteral therapy and a following course of enteral administration.

METHODS: SAH patients were treated with intravenous nimodipine (2 mg/h) during the 1st week after hemorrhage, and on day 8, we switched over to enteral administration (60 mg/4 h), either orally or by gavage. Serum nimodipine concentrations were measured on days 3, 5, 8, 9 and 12. Area under the curve (AUC) was calculated during parenteral and enteral therapy. The data of 15 patients were analyzed retrospectively.

RESULTS: In this study, 157 blood samples were obtained. In seven samples, during the administration by gavage to two patients with high-grade SAH, the serum nimodipine concentrations were negligible. The AUC values during parenteral administration (median 149.3 ng-h/ml) were significantly higher than during oral administration on days 9 (median 92.1 ng-h/ml) and 12 (median 44.1 ng-h/ml) in seven patients (p = 0.030 and p = 0.016, respectively). The AUC values during parenteral administration were significantly higher than during administration by gavage on day 9 in eight patients (median 87.9 and 34 ng-h/ml, respectively, p = 0.001). The AUC values during enteral administration were higher in patients who received nimodine orally than in those who received it by gavage (median 52.3 and 23.1 ng-h/ml, respectively, p = 0.006).

CONCLUSIONS: Enteral administration of nimodipine showed lower bioavailability during the 2nd week after SAH compared to parenteral application during the 1st week. Negligible serum concentrations were even expected when nimodipine was given by gavage in patients with high-grade SAH, thus suggesting that parenteral administration may be the better route in these patients.