Subcutaneous administration of nimodipine improves bioavailability in rabbits.
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.
Laslo, AM; Eastwood, JD; Urquhart, B; Lee, T-Y; Freeman, D
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