Nasal Absorption of the Calcium Antagonist Nicardipine in Rats and Rhesus Monkeys

Abstract

Nicardipine hydrochloride, a highly potent calcium entry channel blocker was administered intranasally to rats and rhesus monkeys. The Intranasal absorption of nicardipine in rats was studied with aqueous vehicles containing 0.1 M citrate buffer pH 3.5, 0.01 M acetate/propylene glycol (90:10 W/W) pH = 5.0, and a similar acetate/propylene glycol system containing sodium taurocholate. Peak plasma levels were found to occur 30 minutes after an Intranasal dose of 1.0 mg/kg, and the fraction absorbed using each of the vehicles described above was determined to be 0.85, 0.54, and 0.82 that of an equivalent Intravenous dose. These Initial screening studies were extended Into a monkey model system, with a similar group of formulations. The results obtained in the monkey were qualitatively similar to the data generated in the rat model with regard to rapid attainment of peak plasma levels and subsequent elimination from the plasma. The major difference between the two animal models studied was the significantly lower systemic availability observed in the monkey.