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Prednicarbate

Authors
  • Spencer, Caroline M.1
  • Wagstaff, Antona J.1
  • 1 Adis International Limited, 41 Centorian Drive, Mairangi Bay, Auckland 10, New Zealand , Mairangi Bay, Auckland 10 (New Zealand)
Type
Published Article
Journal
BioDrugs
Publisher
Springer International Publishing
Publication Date
Jan 01, 1998
Volume
9
Issue
1
Pages
61–86
Identifiers
DOI: 10.2165/00063030-199809010-00006
Source
Springer Nature
Keywords
License
Yellow

Abstract

SynopsisPrednicarbate is a synthetic nonhalogenated moderate to high potency corticosteroid. It is rapidly metabolised during skin permeation to prednisolone.Prednicarbate is indicated for relief of inflammation and pruritus associated with corticosteroid-responsive dermatological disorders such as dermatitis (eczema) [including atopic dermatitis] and psoriasis and can be used in children and elderly patients. Large clinical trials conducted in patients with various dermatoses confirm the efficacy of the drug. Smaller trials, conducted in patients with dermatitis, show prednicarbate generally to have similar activity to comparator corticosteroids. Data concerning use of prednicarbate in psoriasis are more limited, although again the drug demonstrated similar efficacy to the corticosteroids with which it was compared.The tolerability of prednicarbate was generally good, although methods of recording adverse events were not clearly reported in many trials. The atrophogenic potential of prednicarbate appears to be low when no occlusion is used. However, atrophogenic effects increase with occlusion.Therefore, prednicarbate is a useful option for the treatment of corticosteroid-responsive dermatoses and appears to have low atrophogenic potential when used without occlusion.Pharmacodynamic PropertiesPrednicarbate is a synthetic nonhalogenated moderate to high potency corticosteroid that undergoes rapid enzymatic degradation during skin permeation to the active metabolite prednisolone-17-ethylcarbonate. It is indicated for relief of inflammation and pruritus associated with corticosteroid-responsive dermatological disorders such as atopic dermatitis and psoriasis. Galenic formulations of the drug, including the cream, solution and ointment, are generally considered to have good or excellent cosmetic acceptability.Prednicarbate had dose-dependent anti-inflammatory activity in the ultraviolet erythema test and the vasoconstrictor assay in volunteers. This activity was increased under occlusion. The effect of prednicarbate cream 0.25% under occlusion was significantly greater than that of hydrocortisone 1%, significantly less than that of hydrocortisone buteprate 0.1% and similar to that of betamethasone valerate 0.1%. In contrast, without occlusion, the anti-inflammatory activity of prednicarbate cream was less than that of betamethasone valerate, hydrocortisone aceponate and hydrocortisone buteprate and similar to that of hydrocortisone or the prednicarbate vehicle. Prednicarbate 0.25% formulations also had similar anti-inflammatory activity to corresponding formulations of methylprednisolone aceponate 0.1% in volunteers (it appears that no occlusion was used).Prednicarbate has low atrophogenic potential when applied for prolonged periods (generally 4 to 8 weeks) without occlusion in healthy volunteers. Skin thinning was significantly less with prednicarbate cream 0.25% than with clobetasol propionate 0.05%, fluocinolone acetonide 0.025% or betamethasone valerate 0.1% when occlusion was not used. However, when occlusion was used (treatments were applied 3 times weekly for 4 or 6 weeks), skin thinning in prednicarbate recipients was similar to that seen in volunteers receiving clobetasol propionate and betamethasone valerate. Indeed, prednicarbate generally reduced skin thickness by about 10% (not significant) when occlusion was not used and by 20 or 26% (p < 0.05) when occlusion was applied. Long term application of prednicarbate cream 0.25% (6 and 12 months) appeared to cause little skin damage in small numbers of volunteers.Prednicarbate inhibited in vitro growth and proliferation of fibroblasts but had less effect on these parameters than desoximetasone and betamethasone valerate. Similarly, although wound healing in hairless mice and guinea-pigs was inhibited by prednicarbate, the drug had less effect than betamethasone dipropionate (strength and formulation not stated) and hydrocortisone ointment 1.25%.The effects of prednicarbate on the hypothalamic-pituitary-adrenal axis have been assessed only in small numbers of patients or volunteers (n = 5 to 20), although these groups included children, patients with extensive dermatoses (usually >20% of body surface affected) and volunteers who applied the drug to their total body surface. Available data suggest that the drug causes negligible adrenal suppression. An additional study, reported as part of an abstract, also showed prednicarbate cream 0.1% to have no effect on the hypothalamic-pituitary-adrenal axis function of 55 children aged 2 months to 12 years with moderate to severe atopic dermatitis.Hypersensitivity reactions to prednicarbate have been reported in small numbers of patients.Pharmacokinetic PropertiesFew pharmacokinetic data concerning prednicarbate are available. Neither prednicarbate nor its metabolites were detected in the plasma of 8 healthy volunteers who applied, under occlusion, 75mg of prednicarbate cream 0.25% to approximately 50% of their body surface. After oral administration of prednicarbate 40mg, no parent drug was detected in plasma, although the metabolites prednisolone-17-ethylcarbonate and prednisolone were identified. Tests in animal models indicate that after topical application, prednicarbate is metabolised in the skin. Indeed, in vitro studies using human tissue indicate that the drug is rapidly metabolised in the epidermis by keratinocytes.Clinical EfficacyThe efficacy of prednicarbate 0.25% has been demonstrated in a number of non-comparative trials which enrolled between 189 and 1614 patients with various dermatoses (including 1 trial which enrolled 1286 patients aged ≥60 years). The drug was particularly effective in patients with seborrhoeic dermatitis.A long term study (10 to 100 weeks) showed that intermittent therapy with prednicarbate 0.25% (in a variety of galenic formulations) had very good or good efficacy in 92% of 189 patients with various dermatoses. Prednicarbate treatment was required for ≤12 phases per patient and temporary remission was achieved by 89% (mean) of patients over all treatment phases.Prednicarbate ointment 0.25% was more effective than its vehicle alone after twice-daily application for 4 weeks in patients with dermatitis. The efficacy of twice-daily prednicarbate cream or ointment (0.25% where stated) did not differ significantly from that of respective formulations of twice-daily halomethasone 0.5%, fluocortolone monohydrate 0.2% or fluocinolone acetonide (strength not stated) or once-daily methylprednisolone aceponate 0.1%, but was greater than that of fluocortin butyl ester 0.75%. However, when patients with severe disease only were considered, prednicarbate was less effective than halomethasone. Prednicarbate 0.25% also had lower and slower efficacy than amcinonide 0.1% when these agents were applied in a cream base for 2 weeks. A small (n = 21) intra-individual trial showed that clobetasol cream 0.5% provided faster relief than prednicarbate cream 0.25% in about 50% of patients with persistent eczema. Treatment effects with each agent were similar in the remaining 11 patients.Prednicarbate cream 0.1% had efficacy similar to that of betamethasone valerate cream 0.1% and significantly superior to vehicle in 2 well designed clinical trials each conducted in >180 patients.In trials that enrolled children with dermatitis only, prednicarbate 0.25% demonstrated good efficacy, often within 2 weeks. Changes in symptom scores did not differ significantly between prednicarbate and mometasone furoate 0.1%, and prednicarbate and methylprednisolone aceponate 0.1% produced similar response rates in comparative trials. However, patient numbers were usually small in these studies.Prednicarbate 0.25% is also effective in the treatment of psoriasis. In general, efficacy rates of about 70 to 80% were obtained with prednicarbate ointment, fatty ointment or solution. The therapeutic effects of prednicarbate did not differ significantly from those of betamethasone valerate 0.1%, desoximetasone 0.25%, diflucortolone valerate 0.1% or fluocinolone acetonide (strength not stated) in comparative trials, but desoximetasone had a significantly faster onset of action.TolerabilityIt is unclear how adverse event data were obtained in a number of the clinical trials of prednicarbate. Nevertheless, results of these trials suggest that the drug is generally well tolerated. In the 4 clinical studies that specifically considered the presence or absence of signs of skin atrophy, no atrophogenic effects were detected; one of these was conducted in children. Indeed, prednicarbate was associated with few adverse events in children.Several studies reported that no adverse events were observed with cream, ointment or fatty ointment formulations of prednicarbate 0.25%. The most commonly reported adverse events with the drug include erythema, burning, pruritus, skin dryness or irritation. Overall, 3.4% of 1614 patients experienced generally mild adverse events with prednicarbate solution 0.25%, although the incidence was slightly higher (5.3%) in patients with palmoplantar psoriasis than in the general study population. In a long term study (<100 weeks) of intermittent prednicarbate 0.25%, adverse events interrupted therapy in 2.6% of 189 patients.Physicians considered the tolerability of prednicarbate 0.25% to be at least good in >90% of patients. However, serious adverse events occurred when prednicarbate 0.25% was applied to facial skin in 5 patients (4 with probable perioral or periorbital dermatitis) included in 1 report.Adverse events occurred at similar frequency and severity in patients receiving prednicarbate 0.1 or 0.25% and comparator agents.Dosage and AdministrationPrednicarbate is available as 0.25% or 0.1% formulations. It should be gently and sparingly rubbed into affected skin areas once or twice daily. Treatment should be discontinued as soon as control of the disease is achieved. Occlusive dressings may be used in patients with severe or resistant dermatoses, but this increases the risk of local and systemic adverse events. Topical prednicarbate can be used, with care, in children aged ≥1 year.

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