Vasoconstrictor activities and bio-availabilities of seven proprietary corticosteroid creams assessed using a non-occluded multiple dosage regimen;clinical implications

Abstract

The bio-availabilities and activities of commercial creams (Metosyn, Synalar, Betnovate, Locoid, Alphaderm, Dioderm and Efcortelan 1%) were assessed using a multiple dosage regimen vasoconstrictor assay in ten volunteers. The blanching response first increased but then diminished with continued application over a 5-day period: following a 2-day 'resting period', when no steroid was applied, the application sites recovered considerably but tachyphylaxis again resulted from subsequent repeated applications. Acute tolerance occurred with the hydrocortisone formulations (Alphaderm, Dioderm and Efcortelan 1%) in a manner similar to that observed with the potent preparations. Metosyn was significantly more active (P less than 0.05), and Efcortelan 1% was significantly less active (P less than 0.05), than the other formulations. Apart from the reversal of Dioderm and Alphaderm the rank order of preparations was similar to that previously noted in the 6 h occluded single-application vasoconstrictor test. The results may have significance in dosage from design and application for topical corticosteroid formulations.

Possible Dosage Regimens for Topical Steroids, Assessed by Vasoconstrictor Assays Using Multiple Applications

“…1). The in cidence of tachyphylaxis in the second week was less than that demonstrated by Barry and Woodford [2] using the more drastic regimen of three times daily application. The areas under the blanching curves for both weeks were similar, mean values for the first week being 49.1% (range 45.7-54.4%, depending on formulation/regimen) and for the second week, 50.9% (range 45.6-54.3%) of the total values (table I).…”

“…4, 5]. The authors' previous studies using a non-occluded multiple-dosage regi men involved a three times daily application [2]: less frequent administration might pro duce less marked tachyphylaxis. Lack of clinical studies comparing the use of potent topical steroids in twice daily, daily and al ternate-day regimens [3] prompted investi gation of such regimens in the repeated-ap plication skin-blanching test.…”

Increased bioavailability of hydrocortisone dissolved in a cream base

“…Two sites (7 × 7 mm in area) were used on each forearm of each volunteer using a nonoccluded assay design as previously described. 14,15 Each application site was randomly assigned a preparation. A plastic template and an indelible ink marker were used to delineate the application sites.…”

Pharmacology of the Skin II

“…The most widely used in vivo assay of corticosteroid potency is the vasoconstrictor test, which has been refined by BARRY and WOODFORD (1977). The principle of this test is that glucocorticoids, when applied topically under occlusion, will produce blanching of the skin.…”