Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage – a pilot study

Abstract

The pharmacokinetics of nimodipine following enteral administration in the early phase after subarachnoid haemorrhage (SAH) has not been described. If a sufficient absorption could be achieved with enterally administered nimodipine, this would be more feasible dosage form and result in a significant reduction in pharmaceutical costs given that the parenteral formulation of nimodipine currently used is tenfold more expensive than the enteral formulation. This was a pilot study in which 17 patients with aneurysmal SAH were randomly assigned to receive nimodipine within 24 h after initial bleeding either as an 60 mg tablet/suspension at 4-h intervals, or as a continuous intravenous infusion of 2 mg/h. Serum nimodipine concentrations were measured during the 4 h following the first dose, and at 24 and 72 h on a validated gas chromatography mass spectrometer (GC-MS). Nimodipine AUC values (expressed in mug min/ml) were lower in the eight SAH patients receiving enteral nimodipine [AUC(0-4) range: 0.13-5.4 (median: 0.32); AUC(24-28) range: 0.16-6.1 (0.71); AUC(72-76) range: 0.47-20.6 (1.9)] than in the nine patients receiving a continuous intravenous infusion of nimodipine [AUC(0-4) range: 2.4-4.9 (3.4), p=0.059; AUC(24-28) range: 4.7-10.3 (7.3), p=0.001; AUC(72-76) range: 3.4-8.6 (6.9), p=0.001]. In three of five good-grade SAH patients receiving nimodipine tablets the AUC values were comparable to those of the intravenous administration, but in two good-grade patients with tablets and in all three poor-grade (Hunt&Hess, grade IV) SAH patients receiving the suspension, the rate and extent of nimodipine absorption was negligible. This pilot study indicates that the rate and extent of nimodipine absorption following enteral administration in some acute SAH patients could be negligible, and this may particularly be the case in patients with a decreased level of consciousness.