ASSESSMENT OF GLUCOCORTICOID LUNG TARGETING BY EX-VIVO RECEPTOR-BINDING STUDIES IN RATS

Triamcinolone acetonide (TA, 22 mu g) was given to rats by intravenous (IV) injection or intratracheal (IT) instillation. Free glucocor tico id receptors were monitored over time in liver and lung using an ex-vi vo receptor binding technique. After IV administration of a TA solutio n, the reduction of free receptors over time was very similar in lung and liver (AUC(Lung) = 280 +/- 47 %h; AUC(Liver) = 320 +/- 76 %*h). I ntratracheal instillation of the same solution produced time profiles which mirrored those of IV injection (AUC(Lung) = 260 +/- 41 %h; AUC( Liver) = 330 +/- 50 %h). The lack of lung targeting was also reflecte d in the failure to show any significant difference in the pulmonary t argeting factor T (AUC(Lung)/AUC(Liver)) between IV (T = 0.84 +/- 0.18 ) and IT (T = 0.78 +/- 0.03) administration. In contrast, a certain de gree of lung specificity was observed after IT instillation of a gluco corticoid suspension (22 mu g; AUC(Lung) = 160 +/- 135 %h; AUC(Liver) = 65 +/- 91 %h, T = 2.3 +/- 0.5) as indicated by significant differe nces in T between IV injection and IT instillation (p = 0.038). The me thod presented provides a means of simultaneously assessing pulmonary and systemic effects after different forms and routes of administratio n and might be of value in further studying multiple aspects of inhala tion glucocorticoid therapy.