부산대학교 도서관

Ipratropium bromide (3α-hydroxy-8-isopropyl-lαH, 5αH-tropanium bromide(±)-tropate) labeled with 14C was administered orally, intranasally and intravenously to rats and rabbits (5 mg/100μCi/kg) to examine the absorption, distribution and excretion. The radioactivity in rat blood reached to the highest level of 0.024 μg/ml at 3 hr after oral dosing, 0.025 μg/ml at 4 hr after oral dosing under anesthesia and 0.072 μg/ml at 1 hr after intranasal dosing. The area under the blood concentrationtime curve (AUC) within 24 hr after dosing were 0.273 μg•hr/ml after oral dosing, 0.257 μg•hr/ml after oral dosing under anesthesia, 0.622 μg. hr/ml after intranasal dosing and 8.559 μg•hr/ml after intravenous dosing. The cumulative urinary excretion in rats was 3.2 ?? 5.9% of dose after oral dosing and 10.2% of dose after intranasal dosing. The concentration in almost all tissues of rats reached to the highest level during 1 to 6 hr after intranasal administration and 1.9 % of administered radioactivity was retained in nasal cavity at 6 hr after intranasal administration. The plasma protein binding in rats was 27.5%, 29.6% and 78.6% at 1, 6 and 24 hr after intranasal dosing, respectively and less than 10 % of 14C-Ipratropium bromide was bound to the plasma protein during in vitro experiment. The peak blood concentration in rabbits were 0.064 μg/ml at 1 hr after oral dosing and 0.022 μg/ml at 4 hr after intranasal dosing. The AUC within 48 hr after dosing were 1. 105 μg•hr/ml after oral dosing, 0.436 μg•hr/ml after intranasal dosing and 7.141 μg•hr/ml after intravenous dosing. The cumulative urinary excretion in rabbits was 12.7% of dose after intranasal dosing. The plasma protein binding in rabbits was 24.5 %, 29.7 % and 57.1 % at 1, 6 and 24 hr after intranasal dosing and less than 10 % of 14C-Ipratropium bromide was bound to the plasma protein during in vitro study.