Bioavailability of intranasal scopolamine in normal subjects

The bioavailabilily of scopolamine in three dosage forms was compared in 12 healthy nonsmoking male volunteers. Subjects received 0.4-mg doses of scopolamine bromide in intravenous (IV), intranasal (IN), or oral (PO) dosage forms on three occasions, with at least 2 weeks separating the doses. Scopelamine concentrations in plasma were determined with a combined reverse- phase liquid chromatographic-radioreceptor binding assay. Saliva volume and flow rate and percent suppression of control flow rate were determined from each sample. Absorption after IN and PO scopolamine administration was rapid; plasma concentrations [1680 (IN) and 164 pg/mL (PO)] peaked within 1 h of dosing [0.37 (IN) and 0.78 h (PO)], respectively. IN and IV scopolamine suppressed salivary flow rate to similar extents (95% and 99.7%), respectively. Times to reach maximum effect were 1.05 and 0.27 h after IN and IV dosage, respectively. Absolute intranasal bioavailability, calculated from the area under the drug concentration vs time curve, was found to be significantly greater than that of PO scopolamine (83% vs 3.7%, p < 0.05). The IN route may provide a noninvasive, reliable, fast, and effective route for administering scopolamine.