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Methylprednisolone Aceponate

A Review of Its Pharmacological Properties and Therapeutic Potential in the Topical Treatment of Eczema

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Summary

Synopsis

Methylprednisolone aceponate is a nonhalogenated diester of 6α-methylprednisolone which, based on its anti-inflammatory activity, has been classified as a potent glucocorticosteroid. In adults and children with various forms of eczema, methylprednisolone aceponate 0.1% cream, ointment or fatty ointment appears to be as effective as betamethasone valerate 0.1%, hydrocortisone butyrate 0.1% and prednicarbate 0.25% in corresponding formulations; marked improvement or complete remission of signs and symptoms was observed in approximately 90% of patients after 3 to 4 weeks’ therapy. In terms of tolerability, local symptoms (itching, burning, erythema, drying, weeping, papules/vesicles or fissures) were observed in up to 6% of patients following treatment with methylprednisolone aceponate. While rare cases of skin atrophy and telangiectasia have been described, systemic effects have not been seen to date.

Thus, initial findings suggest that methylprednisolone aceponate has potential in the treatment of eczema. At this stage in its development, more extensive clinical experience is necessary to determine whether methylprednisolone aceponate provides additional benefit over other more widely used agents of its class, particularly in terms of possessing a low propensity for systemic effects.

Pharmacodynamic Properties

Methylprednisolone aceponate is a nonhalogenated diester of 6α-methylprednisolone. The introduction of 2 ester groups results in a molecule with increased lipophilicity, and enhanced penetration into skin. Esdmadons of and-inflammatory activity in humans suggest that it is a potent glucocorticosteroid. In humans its atrophogenic potential, as assessed by skin thinning and telangiectasia, appears lower than, or similar to, that of other agents belonging to this class such as betamethasone valerate 0.1% and mometasone furoate 0.1%. Although suppression of plasma Cortisol levels and/or normal circadian pattern of Cortisol release has been observed in some volunteers after daily administration of 30g of methylprednisolone aceponate 0.1% ointment under occlusion for 5 days, inhibition of pituitary-adrenal function was not apparent in patients treated with methylprednisolone aceponate for various dermatoses, even after extended use of the drug for up to 4 months.

Pharmacokinetic Properties

In volunteers, total percutaneous absorption of [14C]methylprednisolone aceponate 0.1% ointment after application of two 400mg doses to an area of 80cm2 on separate days was < 1%.

Methylprednisolone aceponate is extensively metabolised by esterolytic hydrolysis within the skin. Methylprednisolone 17-propionate, which has greater affinity for intracellular corticosteroid receptors than does the parent compound, is the primary metabolite formed. On reaching the systemic circulation, metabolites are mainly inactivated by conjugation with glucuronic acid and subsequently eliminated in the urine; 14C radioactivity is mainly eliminated as methylprednisolone 17-propionate, with a half-life of approximately 16 hours.

Therapeutic Potential

In a total of approximately 1800 patients with various forms of eczema (including atopic dermatitis), comparative data suggest that topical methylprednisolone aceponate 0.1% cream, ointment or fatty ointment is as effective as betamethasone valerate 0.1%, hydrocortisone butyrate 0.1% or prednicarbate 0.25% in its corresponding formulation. Based on subjective rating scales, approximately 90% of patients treated with methylprednisolone aceponate showed complete remission or marked improvement in symptoms after 3 to 4 weeks of therapy; complete remission was observed in 45 to 65% of patients. A similar efficacy profile was observed in children treated for 1 to 3 weeks and in adults with chronic eczema treated for longer periods of 4 to 6 months.

Tolerability

Methylprednisolone aceponate appears to possess a similar tolerability profile to betamethasone valerate 0.1%, hydrocortisone butyrate 0.1% and prednicarbate 0.25%; collated data from approximately 1560 adults and children treated with methylprednisolone aceponate for various types of eczema over 3 to 4 weeks indicate that local symptoms (itching, burning, erythema, drying, weeping, papules/vesicles or fissures) occur in up to 6% of patients. A similar pattern of local adverse events was noted in patients with chronic dermatoses who received long term methylprednisolone aceponate therapy for 4 to 6 months. Although rare cases of atrophy and telangiectasia were described, adverse systemic effects have not been observed to date.

Dosage and Administration

Methylprednisolone aceponate 0.1% cream, ointment or fatty ointment should be applied thinly to affected areas once daily. Currently, manufacturer recommendations indicate that maximum duration of therapy should not exceed 12 weeks in adults or 4 weeks in children.

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Malini Haria & Julia A. Balfour

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Additional information

Various sections of the manuscript reviewed by: A. Cooper, Gosford, New South Wales, Australia; P. Dykes, Department of Dermatology, University of Wales College of Medicine, Cardiff, Wales; J.M. Haigh, School of Pharmaceutical Sciences, Rhodes University, Grahamstown, South Africa; E. Haneke, Department of Dermatology, Ferdinand-Sauerbruch-Klinikum, Elberfeld, Wuppertal, Germany; A.M. Kligman, Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; H.J. Lee, College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, USA; H.I. Maibach, Department of Dermatology, UCSF School of Medicine, San Francisco, California, USA; J-P. Ortonne, Dermatologie, Centre Hospitalier Universitaire de Nice, Hopital ‘Pasteur’, Nice, France; N. Pimpinelli, Clinica Dermosifilopatica II, Università Degli Studi di Firenze, Florence, Italy; E. Rampini, Department of Dermatology, Instituto ‘Giannina Gaslini’, Genoa, Italy.

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Haria, M., Balfour, J.A. Methylprednisolone Aceponate. Clin. Immunother. 3, 241–253 (1995). https://doi.org/10.1007/BF03259059

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