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Both halobetasol propionate and clobetasol 17-propionate exerted very marked antiinflammatory, antiproliferative, and vasoconstrictive effects during evaluation in a range of dermatopharmacologic models. Halobetasol propionate was distinctly more potent than clobetasol 17-propionate in the ultraviolet-induced dermatitis inhibition assay in guinea pigs and in the rat model of oxazolone-induced late inflammatory reaction. Halobetasol propionate was slightly more potent than clobetasol 17-propionate in inhibiting croton oil-induced ear edema in rats and mice and in the mouse model of oxazolone-induced early inflammatory reaction. In the cotton-pellet granuloma assay in rats and the epidermal hyperplasia inhibition assay in guinea pigs, halobetasol propionate was distinctly superior to clobetasol 17-propionate. There was a trend in favor of halobetasol propionate in the cutaneous vasoconstriction assay performed in volunteers with ethanol solutions of halobetasol propionate and clobetasol 17-propionate. In a further vasoconstriction assay, performed with a 0.05% concentration of both halobetasol propionate and clobetasol 17-propionate in cream and ointment formulations, halobetasol propionate ointment yielded the highest blanching score. In a hypothalamic-pituitary-adrenal axis study in volunteers, effects of 0.05% halobetasol propionate ointment and 0.05% clobetasol 17-propionate ointment on serum cortisol levels were similar. The overall efficacy trends demonstrated in these dermatopharmacologic studies are in agreement with predictions made from corticosteroid structure and activity relationships and the results of two clinical trials comparing halobetasol propionate and clobetasol 17-propionate ointments in the treatment of plaque psoriasis.

The effects on the hypothalamic-pituitary-adrenal axis of the ultra-high potency corticosteroid halobetasol in the treatment of psoriasis were evaluated in seven patients with extensive, long-standing plaque psoriasis. Each patient applied 3.5 g halobetasol 0.05% ointment in the morning and evening for 7 days. Morning plasma cortisol levels and 24-hour urinary excretion of 17-hydroxycorticosteroid were determined before and on the last 2 days of treatment; plasma cortisol levels were also determined 4 and 5 days after completion of therapy. Morning plasma cortisol concentrations did not decrease significantly during treatment, and no values were below the normal range. Mean 24-hour urinary 17-hydroxycorticosteroid excretion fell from 6.6 +/- 1.4 mg to 5.1 +/- 1.4 mg. Two patients had mild, localized pruritus and stinging with the initial ointment application. No other adverse cutaneous effects were observed. Halobetasol was also clinically efficacious over the 7 days of treatment, based on evaluation of pruritus, erythema, scaling, and plaque elevation. These results demonstrate no adverse effects of the drug on the hypothalamic-pituitary-adrenal axis at doses that are clinically effective in the management of plaque psoriasis.

The penetration of cephapirin sodium into tissues that are commonly involved in gynecologic infections was studied after administration of a single i.v. dose of 1 g of cephapirin to about 15 patients to undergo gynecologic surgery. Blood and tissue specimens were obtained either 30 or 60 min after the infusion had been completed. Blood levels averaged 16.07 +/- 3.7 and 6.29 +/- 1.6 microgram/ml and mean tissue levels were 7.87 and 6.28 microgram at these two sampling times, respectively. These results suggest that bactericidal levels of cephapirin against sensitive organisms can be achieved in gynecologic tissues.