No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Hydrocortisone 17-butyrate (Locoid®), a thirty-year ongoing innovative drug
Abstract
Since half a century, dermocorticoids represent worthy compounds in dermatological therapy. About thirty years ago, hydrocortisone 17-butyrate was introduced on the Belgian market. This compound combines good efficiency and reduced risk of side effects. Its topical formulations have been enriched over time. The original Locoid lipocream and Locoid Crelo presentations confer remarkable qualities to the product. We report a synopsis of clinical and translational studies devoted to this unique dermocorticoid.
... Как известно, идеальный топический ГК должен обладать выраженным противовоспалительным действием, низкой системной биодоступностью, быстрым началом действия и минимальными местными побочными эффектами. Этим требованиям в полной мере соответствует хорошо изученный в клинических условиях гидрокортизона 17-бутират [11,15,16]. ...
... Последний путь приводил к существенному повышению эффективности: некоторые вещества, полученные синтетическим путем, имели на несколько порядков большую силу, чем естественный гидрокортизон. Однако вскоре стало известно, что галогенизация, придавая более выраженный противовоспалительный эффект, имела больший риск развития побочных явлений [11,15,16]. ...
... У больных, требующих длительной стероидной терапии, и особенно при необходимости нанесении средства на обширные участки кожи, самым безопасным выбором будет стероид, который быстро метаболизируется при попадании в системный кровоток. Такими преимуществами обладает гидрокортизона 17-бутират (Локоид крело, Астеллас, Италия) [15][16][17]. ...
Topical therapy of atopic dermatitis in children is a complex and multifactorial problem. Irrational choice of means of treatment may lead to the deterioration of the child, cause complications of dermatosis, promote the development of «atopic march». Topical treatment’s «Gold standard» is topical corticosteroids. The application of these medicines is not limited to conventional dosage forms such as cream and ointment. The features of the new formulations are presented (emulsions with different lipid concentration), the recommendations on their practical use are stated, the clinical experience of their application in the treatment of children with atopic dermatitis is described.
Atopic dermatitis is under the influence of series of environmental factors. The contact with unsuited cleaning agents and rough textiles can exacerbate pruritus and inflammation. Preventive and adjuvant measures can thus help the care procedures of the disease. Appropriate hygiene measures and the use of emollients are particularly helpful. Clothing measures are also in place. Undergarments and pyjamas made of knitted natural silk are available. Other measures, sometimes corresponding to anecdotal claims--antihistamines, thermal cures, unconventional medicine, probiotics, chinese herbals, essential fatty acids--have not proven their preventive efficacy in atopic dermatitis.
Intertrigo is a common inflammatory disorder of various origins. It can represent a single skin manifestation or be part of a disorder possibly exhibiting specific manifestations on other parts of the body. Hence, intertrigo may represent a sign of a peculiar disease. It may also result from physicochemical aggressions of the skin following occlusion of the large skinfolds particularly in case of stoutness. In this intance, a treatment similar to that of diaper dermatitis can be offered. A paste enriched or not with miconazole nitrate is indicated to prevent or treat most presentations of intertrigo.
A randomized, double-blind, left-right study to compare the therapeutic efficacy and the cosmetic acceptability of the new hydrocortisone 17-butyrate (Locoid®) 0·1% fatty cream application form with desonide (Apolar®) 0·1% ointment was performed in thirty patients suffering from moderate to severe atopic dermatitis. The medications were applied to symmetrical, bilateral skin lesions twice daily for 4 weeks. Both treatments effected highly significant reductions of the score values for the severity of all clinical skin parameters assessed. Score reductions were, however, more pronounced on Locoid-treated sides than on Apolar-treated sides both after 2 and 4 weeks of therapy. It appeared further that clinical efficacy of treatment at completion of the study was also in favour of Locoid-treated sides, indicating that Locoid fatty cream is more effective than Apolar ointment. No serious side-effects were reported during the study.
The expressed patient preferences with respect to cosmetic acceptability of treatments were significantly in favour of Locoid fatty cream, indicating that patients preferred the use of this new galenic formulation over an ointment formulation. It is concluded that the new application form of Locoid, a fatty cream, is a useful and beneficial addition to topical corticosteroid therapy, which will promote patient compliance in a wide range of corticosteroid-responsive skin diseases.
A randomized, double-blind, left-right study comparing the therapeutic efficacy and cosmetic acceptability of the new hydrocortisone 17-butyrate (HCB) 0.1% lipocream application form with betamethasone 17-valerate (BMV) 0.1% cream was performed in 61 patients suffering from dry severe chronic eczema. The medications were applied to symmetrical bilateral skin lesions twice daily for four weeks. Both treatments resulted in highly significant reductions in the values for the severity of all clinical skin symptoms assessed; no statistically significant differences between the two therapies could be demonstrated after two and four weeks of therapy. On completion of the study complete clearance of all skin symptoms was found in 64% of HCB-treated sides and 61% of BMV-treated sides. Here, too, statistically significant differences did not emerge, indicating that both preparations are equally effective in the treatment of dry severe chronic eczema. One patient withdrew from the study after two weeks because of increased redness, scaling, and itching on both sides. No other side effects were observed. The patients' preferences expressed with respect to cosmetic acceptability of both preparations were significantly in favor of HCB lipocream, indicating that patients preferred the use of this new galenic formulation over an ordinary cream formulation.
Thirty patients suffering from psoriasis were treated in a randomized, double-blind, left-right comparative trial with Locoid® (hydrocortisone 17-butyrate) and Betnovate® (betamethasone 17-valerate) creams. Both therapies effected a highly significant reduction in mean score values in desquamation (67% cleared after 4 weeks treatment) and a significant linear improvement on infiltration/erythema. There were no statistically significant differences between the therapies with respect to reduction in mean score values nor with respect to differences in numbers of cases in which a difference was observed between the therapies. Side effects of pruritus or a burning sensation were reported on both treatment sides in 3 patients.
New formulations of topical corticosteroids are developed to provide therapeutic and cosmetic benefits. The proper choice of the vehicle is important because the moisturizing effect of a topical formulation may increase the drug bioavailability and improve the skin barrier function. The effect was studied of eight proprietary corticosteroid formulations on the capacitance and water loss of skin with moderate xerosis. A transient hydration of the stratum corneum was perceptible for 2–4 h after application of some formulations, allowing a ranking of the vehicles according to the cumulative value of capacitance. It is concluded that the range in the changes in the physico-chemical properties of the stratum corneum induced by steroid vehicles is wide. Bioavailability of the drugs and clinical efficacy are likely to be influenced by these differences.
Using the author's technique, the rheological properties of skin are evaluated in situ by the ability of the forearm skin to withstand vertical forces of extension provided by a specially designed stretching device. The vertical extensibility (E) and the ability of the skin surface to regain its initial shape and position after deformation (Biological elasticity, BE) are recorded. Measurements of the rheological properties of skin can be helpful in monitoring therapy and the side effects of drugs. It is a fast and non-traumatizing procedure providing more complete information than the measurement of skin thickness.
Aim To compare the efficacy of a new application form of hydrocortisone 17-butyrate (H17-B), 0.1% topical emulsion (Locoid Crelo®) with that of betamelhasone 17-valerate (BMV) 0.1% scalp lotion (Betnovate ® lotion).
Methods Erythema, induration, scaling, pruritus and overall severity of the disease were assessed in 136 patients with moderately severe psoriasis of the scalp at the start and after two and four weeks of therapy. In addition, the effect of the Crelo® steroid-free vehicle was assessed in 12 other patients by dry dermoscopy and squumometry.
Results Although both treatments induced a prominent overall improvement, this improvement was significantly better in the H17-B-treated group. H17-B emulsion was superior in the reduction of scaling and overall severity after two weeks, and reduction of scaling, induration, overall severity and total symptom score after four weeks. Cosmetic acceptability also favoured H17-B emulsion. This is probably related to the emollient effect which was shown after a one-week treatment with the steroid free emulsion alone.
Conclusion The innovative H17-B emuslion is an efficient addition to topical corticosteroid therapy of psoriasis; it is especially suitable for the treatment of the scalp and other hairy parts of the body.
Eczema craquelé can be induced by repeated open application of a topical glucocorticoid, viz. 0.05% clobetasole 17-propionate cream. This might not be invariably due to the active component. Comparison of the skin surface roughness as assessed by profilometry and as expressed by RZDIN showed a decrease after repeated open application of 0.1% betamethasone 17-valerate cream and 0.25% prednicarbate cream, but an increase following the vehicle of the latter preparation. Thus commercial oil-in-water emulsion preparations seem to be potentially injurious to human skin, though this may be masked when a glucocorticoid is added.
Topical corticosteroids may induce local and systemic adverse reactions. Some of the corticosteroids are at low risk to induce several manifestations, but gross overdosage or misuse of the most potent steroids are responsible for a number of adverse reactions. An overview of the effects of topical corticosteroids upon the different structures of human skin is presented here.
Recently several attempts have been made to develop glucocorticoids which show less pronounced side effects. We intended, therefore, to use experimental systems to examine the influence of newly developed nonhalogenated glucocorticoids and conventional fluorinated congeners, demonstrating similar anti-inflammatory activity in vivo, on biosynthetic capacities of human fibroblasts. Fibroblasts were kept in monolayer cultures and exposed to different concentrations of the active compounds for 6 days to analyze the influence on proliferation. Chemotaxis of fibroblasts was studied in blind well Boyden chambers. Fibroblast-conditioned medium was used as chemoattractant. All glucocorticoids tested influenced fibroblast proliferation at high (10(-5) M) and low (10(-9) M) concentration. Yet the effect was clearly more marked with fluorinated compounds. Basically, the same applied for chemotaxis. At the low concentration, however, nonfluorinated glucocorticoids exerted almost no influence. These results suggest that modifications of steroidal structure can specifically influence their effects on biosynthetic capacities of fibroblasts.
Objective: Squamometry is a non-invasive test allowing a reproducible rating of cutaneous xerosis including atopic dermatitis lesions. The method was used to compare the efficacy of proprietary topical corticosteroids in alleviating signs of atopic xerosis.
Results: The steroid compounds and their vehicles improve the texture of the stratum corneum at different rates after treatment for 1 week. Some differences in efficacy may be explained by the nature of the vehicle, which enhances the basic pharmacological activity of the corticosteroid itself.
Immunopharmacology is one of the most dynamic areas in pharmacology encompassing classical immunosuppressive drugs which reveal completely new clues concerning their mode of action as well as novel molecular biology approaches for treating inflammatory and autoimmune diseases, infections and cancer. This article focuses on transcription factors that regulate cell activities involved in immune and inflammatory cell responses and how traditional anti-inflammatory compounds such as glucocorticoids, cyclosporins, tacrolismus and salicylates interfere with the activation cascades triggering the transcription factors. Moreover, promising new initiatives for selective therapeutics including recombinant anti-inflammatory cytokines and proinflammatory cytokine antagonists, and gene therapy will be presented.
Seborrheic dermatitis is a corticosteroid-responsive condition. Topical corticosteroids exhibit distinct activities according to the type and cellular site of action of the hormone and its vehicle. The latter influences not only drug penetration, but also the structure and function of the horny layer.
The present study compared the early response of seborrheic dermatitis to two topical corticosteroids using objective quantifications of the stratum corneum alterations.
Squamometry was used to supplement the clinical assessment of the therapeutic activity of 0.1% hydrocortisone butyrate in an oil-in-water emulsion (Locoid Crelo) and 0.05% betamethasone 17-21 dipropionate lotion (Diprosone lotion).
The hydrocortisone butyrate formulation had a faster onset of efficacy as documented by a greater improvement of lesions after a 1-week twice-daily treatment. Clearance or marked improvement was observed in the two treatment groups at completion of the 2-week trial.
As the ranking of the clinical efficacy was not predicted by the intrinsic anti-inflammatory potency of the steroids, it is suggested that the vehicle contributed itself to the global in vivo efficacy. The anti-inflammatory action of hydrocortisone butyrate appears to be synergistically implemented by the emollient effect of the specially designed oil-in-water emulsion.
The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristics of this steroid, a new compound created according to an identical concept, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halogenated monoester desoximetasone 21-cinnamate (DCE) were tested and compared to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammatory prospectively, Whereas PC and PEP inhibited 1 alpha and 11-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly affected by the conventional glucocorticoids BMV and DM, but also by DCE, The minor unwanted effect of PC and PEP on fibroblasts was also reflected by their low influence on cell proliferation as derived from H-3-thymidine incorporation. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticolds, In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of 11-1 alpha) and antiproliferative effects in fibroblasts (suppression of Il-la and 11-6; 3H-thymidine incorporation) was analyzed. Here, PC is revealed as the only glucocorticoid with an improved benefit/risk ratio. Native PEP is shown to be almost ineffective and DCE presents exactly the opposite features of PC. It is tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts. Copyright (C) 2000 S.Karger AG, Basel.
Corticosteroids are widely used for the treatment of inflammatory skin disorders. However, systemic and local adverse drug reactions, especially skin atrophy, are potential complications that limit their use. Several attempts have been made to increase the safety of topical corticosteroid treatment, including new application schedules, special vehicles and new agents.
In particular, the group of hydrocortisone and prednisolone double esters, with prednicarbate as the first and most often prescribed representative, seem to be equipotent alternatives to the gold standard betamethasone 17-valerate with respect to anti-inflammatory activity. At the same time, these new agents induce less skin atrophy, which may result from a unique skin metabolism and a specific influence on the cytokine network in the epidermis and dermis.
On the basis of these effects, a new approach to in vitro quantification of the benefit-risk ratio has been developed. As already suggested by investigations in human volunteers, the benefit-risk ratio of the new compounds appears to be increased. Therefore, recent research has focused on drugs that selectively modulate cytokine release.