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[Method for evaluating pulmonary clearance in mice and its pharmacological applications]
H Kai1, A Ishibashi, K Takahama
1Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Abstract:
The purpose of this study was to develop a method for evaluating pulmonary clearance in mice that inhaled aerosolized 99mTc-labeled human serum albumin (33mTc-HSA). Mice were ventilated with an aerosol of 99mTc-HSA for 10 min with an ultrasonic nebulizer in an acrylic chamber. Pulmonary clearance was estimated from lung retention ratio at various times after inhalation of 99mTc-HSA. Lung retention ratios in mice were 72.4 +/- 3.3% at 1 hr, 60.1 +/- 2.3% at 3 hr and 34.8 +/- 2.0% at 24 hr after inhalation of 99mTc-HSA, similar to the previous results obtained in humans by cinescintigraphy. The data were analyzed on the basis of two-compartment model. Mabuterol, a beta 2-adrenoceptor agonist, stimulated the pulmonary clearance. In contrast, metyrapone, an adrenal 11-beta steroid hydroxylase inhibitor, suppressed the clearance with a decreased corticosterone content in plasma. These findings suggest that the developed method is useful for evaluating the pharmacological effects on pulmonary clearance.