Bioavailability study of nimodipine in rabbit subarachnoid hemorrhage
Objective: To observe the bioavailability of subcutaneous injection of nimodipine and oral administration of nimodipine in healthy rabbits and SAH rabbits, and determine whether subcutaneous administration is superior to oral administration and to target serum concentration.Methods:36 adult male NZW rabbits were divided into 6 groups (n=6) by random number table method:oral nimodipine group (5 mg/kg and 15 mg/kg), subcutaneous injection of nimodipine group (2.5 mg/kg, 5mg/kg,15 mg/kg), SAH+ subcutaneous injection of nimodipine group (2.5 mg/kg), plasma concentrations of nimodipine in each group were measured and statistical analysis was performed. Results: Oral administration of 15 mg/kg of nimodipine produced a higher Tmax and increased Cmax, which was also greater than 5 mg/kg. The time to peak plasma concentration (Tmax) observed after subcutaneous administration had an opposite trend, with 15 mg/kg resulting in a lower Tmax and a lower AUC tendency than 5 mg/kg. (2) Compared with oral administration, the average concentration of nimodipine in the subcutaneous group was significantly greater than 7 ng/mL (P<0.01), and the plasma concentration of nimodipine remained above 7 ng/mL for significantly longer than oral administration (P<0.01). (3) The Cmax, Tmax and AUC values of nimodipine in healthy NZW rabbits were not significantly different from those measured by subcutaneous injection of 5 and 15 mg / kg (P>0.05). There was no significant difference between healthy NZW rabbits (12.9±10.0) ng/mL and SAH (11.8±4.6) ng/mL NZW rabbits at the target level of treatment with an average nimodipine concentration of 7 ng/mL measured at 24 h (P>0.05). Conclusion: Subcutaneous administration of nimodipine is superior to oral nimodipine and can maintain the plasma level of nimodipine at 7 ng/mL after 24 h,which can help to study the mechanism of nimodipine in delaying vasospasm after SAH treatment.