In rabbits, fetal weight reduction and cleft palate were observed at a fluticasone propionate dose approximately times the MRHDID for adults (on a mg/m² basis at a maternal subcutaneous dose of 4 mcg/kg/day). However, no teratogenic effects were reported at fluticasone propionate doses up to approximately 20 times the MRHDID for adults (on a mg/m² basis at a maternal oral dose up to 300 mcg/kg/day). No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration [see CLINICAL PHARMACOLOGY ].
The precise mechanism through which fluticasone propionate affects rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. In 7 trials in adults, fluticasone propionate nasal spray has decreased nasal mucosal eosinophils in 66% of patients (35% for placebo) and basophils in 39% of patients (28% for placebo). The direct relationship of these findings to long-term symptom relief is not known.