The intranasal absorption of nicardipine hydrochloride was characterized in an in vivo rat model system in which the normal mechanisms of mucociliary clearance and drainage of an instilled dose were not physically altered. The results obtained in this manner, therefore, are expected to be predicative of the delivery and absorption dynamics exhibited in the nasal mucosa of primates and humans. Intranasal delivery of nicardipine was studied in male rats using this model on single-dose administration of 1.0 mg/kg, and compared with both oral and intravenous administration. The effect of the addition of a viscosity agent, hydroxyethyl cellulose, on plasma levels following nasal delivery was also examined. Nicardipine plasma levels were determined by a rapid and specific reversed-phase HPLC method with electrochemical detection that employed nifedipine as an electroactive internal standard in the analysis. The limit of quantitation for nicardipine at 1.0 V versus Ag/AgCl was 8 ng/mL and the linear dynamic range was 15-150 ng/mL. Following intravenous administration the area under the plasma concentration curve was 5110 ng . min/mL as compared to 3730 ng . min/mL following intranasal dosing. This corresponds to a bioavailability of 73%. The addition of a viscosity agent to the nasal formulation was found to give a slight but statistically insignificant increase in the systemic availability (77%). Plasma levels of nicardipine following oral administration (1.0 mg/kg) were determined to be below the limit of quantitation of the analytical technique. These results therefore suggest that nasal delivery of nicardipine is a viable and efficient route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)