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 ticoid receptors were monitored over time in liver and lung using an ex-vivo receptor binding technique. After IV administration of a TA solution, the reduction of free receptors over time was very similar in lung and liver (AUC(Lung) = 280 +/- 47 %*h; AUC(Liver) = 320 +/- 76 %*h). Intratracheal 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 reflected in the failure to show any significant difference in the pulmonary targeting 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 degree of lung specificity was observed after IT instillation of a glucocorticoid suspension (22 mu g; AUC(Lung) = 160 +/- 135 %*h; AUC(Liver) = 65 +/- 91 %*h, T = 2.3 +/- 0.5) as indicated by significant differences in T between IV injection and IT instillation (p = 0.038). The method presented provides a means of simultaneously assessing pulmonary and systemic effects after different forms and routes of administration and might be of value in further studying multiple aspects of inhalation glucocorticoid therapy.