| Little information is available regarding the biopharmaceutical factors that govern pulmonary targeting. Pharmacokinetics/pharmacodynamic simulations have shown that pulmonary targeting can be improved by optimization of dose and drug release rate. Liposomes were used as a model dosage form to show the relevance of dose and release rate on pulmonary targeting in in vivo situations. Liposomes were composed of two phospholipids and triamcinolone acetonide phosphate (TAP-lip). TAP-lip and the drug in solution were administered intratrachealy (IT) into anesthetized rats. Pulmonary targeting was determined by simultaneously monitoring receptor occupancy in lung and liver. The IT administration of the TAP-lip formulation resulted in higher pulmonary targeting and longer mean pulmonary effect times (MET) than that after the IT administration of the drug in solution. Thus, liposomes may represent a valuable approach to optimize the delivery of glucocorticoids via topical administration. The pharmacokinetics and pharmacodynamics of triamcinolone acetonide (TA) after IT and intravenous (IV) administration of TAP-lip, and after IT instillation of the drug in solution, were also investigated. Plasma and lung TA concentrations were determined by HPLC/RIA. No changes in the pharmacodynamics (EC... |
