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.
Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti- inflammatory activity of the topical corticosteroids, in general, is unclear However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins , collectively called lipocorins It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid Arachidonic acid is released from membrane phospholipids by phospholipase A 2 .
The most common side effect of topical corticosteroid use is skin atrophy. All topical steroids can induce atrophy, but higher potency steroids, occlusion, thinner skin, and older patient age increase the risk. The face, the backs of the hands, and intertriginous areas are particularly susceptible. Resolution often occurs after discontinuing use of these agents, but it may take months. Concurrent use of topical tretinoin (Retin-A) % may reduce the incidence of atrophy from chronic steroid applications. 30 Other side effects from topical steroids include permanent dermal atrophy, telangiectasia, and striae.