In general, preferred compositions of the present invention contain up to about 5% by weight of a corticosteriod, up to about 60% by weight drying agent, one or more optional ingredients (for example, one or more anti-itch agents; anti-foaming agents; buffers, neutralizing agents, and agents to adjust pH; coloring agents and decoloring agents; emollients; emulsifying agents, emulsion stabilizers and viscosity builders; humectants; odorants; preservatives, antioxidants, and chemical stabilizers; solvents; and thickening, stiffening, and suspending agents), and a balance of water or solvent.
In a Phase 2 HPA clinical study [see Pharmacodynamics ], pharmacokinetics was evaluated in a subgroup of 12 adult subjects. On Day 8, blood was taken just prior to and at 1, 2, 4, 6, 8, and 12 hours following the last application. Plasma concentration of halobetasol propionate was measureable in all subjects. Based on the geometric mean plasma concentrations at 12 hour post-application across time, steady-state was achieved by Day 8. The mean (±standard deviation) Cmax concentrations for ULTRAVATE lotion on Day 8 was ± pg/mL, with the corresponding median Tmax value of 3 hours (range 0 – 6 hours); mean area under the halobetasol propionate concentration versus time curve over the dosing interval (AUCτ) was 1632 ± 1147 pg•h/mL.
Fluticasone propionate is a highly selective agonist at the glucocorticoid receptor with negligible activity at androgen , estrogen , or mineralocorticoid receptors , thereby producing anti-inflammatory and vasoconstriction effects. It has been shown to have a wide range of inhibitory effects on multiple cell types (. mast cell , eosinophil , neutrophil , macrophages , and lymphocytes ) and mediators (. histamine , eicosanoids , leukotrienes , and cytokines ) involved in inflammation . Fluticasone propionate is stated to exert a topical effect on the lungs without significant systemic effects at usual doses, due to its low systemic bioavailability .