Precise Evaluation of Topically Applied Corticosteroid Potency: Modification of the Stoughton-McKenzie Assay
TL;DR: A Vasoconstrictor assay of extreme sensitivity and high precision that can be used to develop important information relating chemical structure and vasoconstriction following topical application to normal skin.
Abstract: Strict control of experimental variables yields a vasoconstrictor assay of extreme sensitivity and high precision that can be used to develop important information relating chemical structure and vasoconstriction following topical application to normal skin. In this assay fluocinolide has about five times the potency of the standard fluocinolone acetonide while triamcinolone acetonide and betamethasone valerate have approximately the same activity as fluocinolone acetonide. Hydrocortisone with only one thousandth the activity of fluocinolone acetonide is at the lower limit of sensitivity of the assay.
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TL;DR: The high safety margin of inhaled therapy with GCSs has encouraged an increasingly widespread use of these compounds in patients with moderate to severe asthma over the past 20 years, and especially where high firstpass metabolism to inactive compounds in the liver has been demonstrated.
Abstract: Since its development in the early 1950% glucocorticosteroid (GCS) therapy has been an important and often life-saving form of therapy in patients with severe asthma. The long-term use of systemic GCS therapy is, however, limited by major unwanted effects These include adrenal suppresdion, adverse changes in skin, bone and other connective tissues, and growth impairment in children. The severe systemic side-effects of long-term oral GCS therapy stimulated the development of GCS preparations that could be inhaled, in the hope of achieving a local effect in the lungs without a significant risk of unwanted systemic effects The initial inhaled therapy with compounds such as dexamethasone proved disappointing because the GCSs used had inadequate topical potency, and they were not rapidly metabolised to inactive compounds by the liver. The balance of wanted and unwanted effects changed greatly when the topically potent inhaled GCSs such as beclomethasone dipropionate (BDP) and budesonide (BUD) were introduced. This shows especially where high firstpass metabolism to inactive compounds in the liver has been demonstrated, as with BUD and fluticasone propionate (FP). The high safety margin of inhaled therapy with GCSs has encouraged an increasingly widespread use of these compounds in patients with moderate to severe asthma over the past 20 years Many S. Pedersen', P. O'Byme2
365 citations
TL;DR: These medications have marked variability in their formulations, which may increase their adverse event profile for specific procedures, and the administering radiologist should be aware of these potential effects and how to reduce their occurrence.
Abstract: Corticosteroids and local anesthetics have significant variability in their formulations that may increase their adverse event profile for specific procedures.
215 citations
TL;DR: This review presents considerations which can be employed during the development of a semi-solid topical generic product to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production.
Abstract: This review presents considerations which can be employed during the development of a semi-solid topical generic product. This includes a discussion on the implementation of quality by design concepts during development to ensure the generic drug product has similar desired quality attributes to the reference-listed drug (RLD) and ensure batch to batch consistency through commercial production. This encompasses the concept of reverse-engineering to copy the RLD as a strategy during product development to ensure qualitative (Q1) and quantitative (Q2) formulation similarity, as well as similarity in formulation microstructure (Q3). The concept of utilizing in vitro skin permeation studies as a tool to justify formulation differences between the test generic product and the RLD to ensure a successful pharmacodynamic or clinical endpoint bioequivalence study is discussed. The review concludes with a discussion on drug product evaluation and quality tests as well as in vivo bioequivalence studies.
209 citations
TL;DR: The vasoconstrictor assay is an inexpensive and reliable method for screening glucocorticosteroid formulations for clinical activity in psoriasis.
Abstract: • A large group of glucocorticosteroid formulations were assayed by the vasoconstriction test in normal skin sites and paired comparison studies in patients with psoriasis. Excellent correlation between the vasoconstriction assay and selected paired comparison studies occurred in 20 of 23 instances. In three instances, involving two glucocorticosteroid formulations tested, correlation was absent. The vasoconstrictor assay is an inexpensive and reliable method for screening glucocorticosteroid formulations for clinical activity in psoriasis. (Arch Dermatol1985;121:63-67)
191 citations
TL;DR: The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) was demonstrated by immunohistochemistry in skin biopsy samples from healthy volunteers and from patients with psoriasis and eczema as mentioned in this paper.
181 citations
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TL;DR: A simple method for assessing the percutaneous absorption of steroid preparations is suggested using vasoconstriction as an index of absorption, occlusion of the skin surface with Saran Wrap results in a 100-fold difference in absorption over simple topical application.
Abstract: A simple method for assessing the percutaneous absorption of steroid preparations is suggested. Using vasoconstriction as an index of absorption, occlusion of the skin surface with Saran Wrap results in a 100-fold difference in absorption over simple topical application.
610 citations
TL;DR: It is concluded that, despite its low precision, the vasoconstriction assay is of value for screening potential topically active anti-inflammatory steroids.
Abstract: Betamethasone and 23 of its esters and ortho-esters, assayed topically on healthy human subjects, had vasoconstrictor activities ranging from 0.1% to 400% of that of a standard steroid, fluocinolone acetonide. Compared with the standard in ointments, betamethasone 17,21 - methyl - ortho - valerate and betamethasone 17-valerate showed promising activity in the occlusion treatment of psoriasis. It is concluded that, despite its low precision, the vasoconstriction assay is of value for screening potential topically active anti-inflammatory steroids. Vasoconstriction assays should be designed to allow for differences in sensitivity between subjects and between sites of steroid application.
105 citations
TL;DR: FA penetrates skin better than F and is also more potent as a vasoconstrictor and FAA is superior to FA in vasconstriction but about the same in ability to penetrate skin.
Abstract: The glucocorticosteroids, (1) fluocinolone (F), (2) fluocinolone acetonide (FA), (3) fluocinolone acetonide acetate (FAA), (4) betamethasone 17-valerate (BV), and (5) betamethasone (B) were tested for vasoconstrictor potency in vivo and ability to penetrate human and hairless mouse skin in vitro. BV and B penetrate skin at the same rate but are different by over 100-fold with regard to vasoconstrictor potency. FA penetrates skin better than F and is also more potent as a vasoconstrictor. FAA is superior to FA in vasoconstriction but about the same in ability to penetrate skin.
85 citations
TL;DR: The results showed that for six of the eight steroids tested, the "ranking orders" for systemic activity in rats and topical activity in man agreed.
Abstract: To the Editor.— That there are discrepancies between the relative systemic activities of anti-inflammatory steroids in rats and man is well known. In our article "Vasoconstrictor and Systemic Activities of Topical Steroids" 1 we were concerned to demonstrate a correlation, if one existed, between systemic activity in animals and topical activity in man. Our results showed that for six of the eight steroids tested, the "ranking orders" for systemic activity in rats and topical activity in man agreed. The exceptions were betamethasone which had a higher and betamethasone 17-valerate which had a lower systemic ranking in rats than would have been expected from their topical activities in man. Dr. Burdick 2 states that the topical activity of betamethasone 17-valerate, as measured by several other assays in rats, is also substantially below that of betamethasone and implies that we neglected to give this information in our article. We have
39 citations