Subcutaneous administration of nimodipine improves bioavailability in rabbits

• Published in: Journal of neuroscience methods Vol. 139; no. 2; pp. 195 - 201
• Main Authors: Laslo, Amanda M., Eastwood, James D., Urquhart, Brad, Lee, Ting-Yim, Freeman, Dave
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.10.2004
• Subjects: Animals; Bioavailability; Biological Availability; Cerebral vasospasm; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Nimodipine; Nimodipine - administration & dosage; Nimodipine - blood; Nimodipine - pharmacokinetics; Rabbits; Subarachnoid hemorrhage; Subcutaneous injections; Cerebral vasospasm; Bioavailability; Nimodipine; Subarachnoid hemorrhage; Subcutaneous injections
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2004.04.030

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.