Subcutaneous administration of nimodipine improves bioavailability in rabbits

Abstract

We compared subcutaneous and oral methods of nimodipine administration to determine a method of nimodipine administration that maintained serum levels at or above the optimal therapeutic concentration (7 ng/ml). Plasma concentrations of nimodipine were measured in New Zealand White rabbits (2.6–3.9 kg). First, peak plasma concentration ( C max), time to reach peak plasma concentration ( T max), and area under the curve (AUC) parameters were calculated and compared between animals receiving oral or subcutaneous nimodipine (5–15 mg/kg). Next, plasma concentrations were measured 24 h after subcutaneous administration of 2.5 mg/kg of nimodipine in healthy animals and animals with experimentally induced SAH. C max, T max and AUC parameters were significantly greater for subcutaneous compared to oral nimodipine administration, irrespective of dose. Mean nimodipine concentrations at 24 h were >7 ng/ml in both healthy animals (12.9 ± 10.0 ng/ml) and in animals with SAH (11.8 ± 4.6 ng/ml) that received 2.5 mg/kg of subcutaneous nimodipine. In this model, the subcutaneous method of nimodipine administration consistently maintains plasma levels at or above the optimal therapeutic concentration, whereas oral administration fails to do so.