SAFETY AND TOLERANCE OF TROSPIUM CHLORIDE IN THE HIGH-DOSE RANGE

The safety and tolerance of increasing single oral doses of 20, 40, 80 , 120, 180, 240 and 360 mg trospium chloride (Spasmo-lyt(R), CAS 10405 -02-4) were investigated in 29 healthy male volunteers in a double-bli nd placebo-controlled study Blood pressure, heart rate, ECG, pupillary diameter, salivary secretion, and subjective reports of tolerance rev ealed no essential differences between placebo and trospium chloride i n doses up to 120 mg. Starting with single doses of 180 mg, anticholin ergic effects were observed with increasing intensity, i.e., dilatatio n of the pupils, reduction of salivary flow, and increase of heart rat e. While the highest administered dose of 360 mg trospium chloride did not cause any relevant changes of vital parameters (blood pressure, p ulse, ECG), it was subjectively rated as quite unpleasant. The data sh ow that trospium chloride is well tolerated in single oral doses well above the current therapeutic daily dose of up to 40 mg.