Investigation of the pharmacokinetics of clobetasol propionate and clobetasone butyrate after a single application of ointment

Abstract

Summary Using new radioimmunoassay methods, the plasma levels of clobetasol propionate and clobetasone butyrate have been measured following application of ointment to in‐patients with psoriasis or eczema. A single application of 25 g of clobetasol propionate 0·05% ointment caused a rapid rise in plasma clobetasol propionate level during the first 3 h. The level fell gradually but was still appreciable 48 h afterwards. Conversely, the plasma cortisol level fell rapidly after application and remained depressed, not rising to baseline levels until 96 h afterwards. A single application of 30 g of clobetasone butyrate 0.·05% ointment resulted in a measurable rise in clobetasone butyrate levels during the first 3 h but then the levels fell gradually. The concentrations were approximately ten times lower than those of clobetasol propionate. The normal diurnal variation in plasma cortisol levels was not affected.

Liquid chromatography–tandem mass spectrometric assay for clobetasol propionate in human serum from patients with atopic dermatitis

“…used by Hehir et al [3]. As far as we know, other assays for systemic levels of clobetasol propionate have not been published hitherto.…”

“…The development and validation of a sensitive bioanalytical assay for clobetasol propionate in human serum using LC-triple quadrupole MS is reported hereafter. The topical use of clobetasol propionate leading to low systemic serum levels (approximately 1 ng/ml, 24 h after treatment [3]) particularly demands the high sensitivity of the presented method.…”

“…1) is a potent topical corticosteroid often used for the treatment of severe, active atopic dermatitis. Although clobetasol propionate is highly effective in controlling this disease, percutaneous absorption of the drug during daily application of 20-30 g Dermovate ® ointment (0.05%, w/w clobetasol propionate) can lead to suppression of the adrenal gland function with a decrease in cortisol production [1][2][3]. The amount of percutaneous absorption of clobetasol propionate, and the effect on the adrenal gland, probably depends on many factors such as the extent of body surface affected by atopic dermatitis, the mode of application and the amount used per day [4].…”

The potency of clobetasol propionate: Serum levels of clobetasol propionate and adrenal function during therapy with 0.05% clobetasol propionate in patients with severe atopic dermatitis

“…However, highly potent topical corticosteroids such as CLO may behave differently since a single application of 20-30 g CLO ointment induces low serum cortisol levels. The biological half-life of CLO is unknown, but it has been shown that cortisol levels remain low until 96 hours after a single application of 25 g CLO in patients with eczema or psoriasis (5). The biological half-life of prednisolone is 12-36 hours (10).…”

“…Peak levels of CLO were observed between 6 hours and 9 hours after application. The detection of CLO levels was paralleled by a decrease in cortisol levels reaching a nadir 9 hours after application (5).…”