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The inhalation of atropine sulfate from a pressurized metered-dose inhaler was investigated in a nonrandomized four-period rising-dose study. Eight healthy, nonsmoking subjects received 1.7, 3.4, and 5.2 mg of atropine sulfate by inhalation and 1.67 mg of atropine free base (equivalent to 2 mg of atropine sulfate) by intramuscular (i.m.) injection. Serum atropine sulfate concentrations were measured over a 24-h period by gas chromatography/mass spectrometry. Mean serum concentrations increased nonproportionally as the inhaled dose increased. Mean peak concentrations were 4.9, 6.1, and 7.9 ng/ml for the inhaled doses and 8.4 ng/ml for the i.m. dose. Typical anticholinergic effects were seen after all doses.