Results of comparative metabolic analysis of topical drug formulations of methylprednisolone aceponate in vivo

DOI: https://doi.org/10.29296/25877305-2021-07-15
Download full text PDF
Issue: 
7
Year: 
2021

M. Nesterov(1), D. Khvostov(2), R. Ageldinov(1) (1)Scientific Center for Biomedical
Technologies of the Federal Medical and Biological Agency of Russia, Moscow Region, Svetlyye Gory (2)V.M.
Gorbatov Federal Scientific Center for Food Systems Russian Academy of Sciences, Moscow

Methylprednisolone aceponate (MPA) is the latest glucocorticosteroid molecule developed for topical use, having advantageous ratio of safety and efficacy. Peculiarity of MPA is it’s biotransformation after the application when primary MPA is transformed into more active metabolite methylprednisolone 17-propionate (17-MPP). This ensue the definition of metabolic profile – cutaneous concentration of 17-MPP after the application and MPA/17-MPP ratio (metabolic index). After the patent expiration appeared generic MPA drugs which didn’t pass through the full cycle of clinical trials. Metabolic profile of these generics and it’s equivalence to the original product is unknown. In the frames of this research the detection of MPA and it’s active metabolite 17-MPP after the application to the skin of laboratory animals (mini-pigs) was performed via HPLC-MS at several time-points. It was elicited that maximum 17-MPP concentration corresponds to maximum concentration of MPA, thus reflecting the correlation between cutaneous concentration of major metabolite and MPA local transformation. The absolute maximum of 17-MPP concentration and metabolic index was observed for the original drug Advantan® cream 0.1%, overwhelming same parameters for generic cream. This may be the result of differences in vehicles. The elicited metabolic profile differences potentially can question the equivalence of the original drug and generics.
Keywords: 
dermatology
pharmacology
methylprednisolone aceponate
methylprednisolone propionate
Advantan®
referent drug
generic
metabolic profile
metabolic index

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat или click here to download the PDF file.

References: 
  1. Levina Ju.G., Alekseeva A.A., Vishneva E.A. i dr. Osobennosti naruzhnoj terapii atopicheskogo dermatita u detej: rol' metilprednizolona atseponata. Pediatricheskaja farmakologija. 2014; 11 (5): 52–8 [Levina Yu.G., Alekseeva A.A., Vishneva E.A. et al. Peculiarities of external therapy of atopic dermatitis in children: role of methylprednisolone aceponate. Pediatric pharmacology. 2014; 11 (5): 52–8 (in Russ.)]. DOI: 10.15690/pf.v11i5.1165
  2. Ruzicka T. Methylprednisolone aceponate in eczema and other inflammatory skin disorders – a clinical update. Int J Clin Pract. 2006; 60 (1): 85–92. DOI: 10.1111/j.1368-5031.2005.00754.x
  3. Zaumseil R.P., Fuhrmann H., Kecskes A. et al. Methylprednisolone aceponate (Advantan) – an effective topical corticoid therapy with few side effects. Jahrb Dermatol. 1992; 3: 247–63(in German).
  4. Fritsch P. Clinical experience with methylprednisolone aceponate (MPA) in eczema. J Dermatolog Treat. 1992; 3 (Suppl. 2): 17–9. DOI: 10.3109/09546639209092768
  5. Luger T., Loske K.D., Elsner P. et al. Topical skin therapy with glucocorticoids-therapeutic index. J Dtsch Dermatol Ges. 2004; 2 (7): 629–34 (in German). DOI: 10.1046/j.1439-0353.2004.03626.x
  6. Volkova E.N., Lange D.A., Rodina Ju.A. i dr. Metilprednizolona atseponat v kompleksnoj terapii hronicheskih dermatozov: analiz takticheskih oshibok primenenija. Klinicheskaja dermatologija i venerologija. 2010; 8 (5): 97–102 [Volkova E.N., Lange D.A., Rodina Iu.A. et al. The use of methylprednisolone aceponate in the combined treatment of chronic dermatoses: analysis of erroneous applications. Klinicheskaya Dermatologiya i Venerologiya. 2010; 8 (5): 97–102 (in Russ.)].
  7. Blume-Peytavi U., Wahn U. Optimizing the treatment of atopic dermatitis in children: a review of the benefit/risk ratio of methylprednisolone aceponate. J Eur Acad Dermatol Venereol. 2011; 25 (5): 508–15. DOI: 10.1111/j.1468-3083.2010.03942.x
  8. Korotkij N.G., Taganov A.V., Shimanovskij N.L. Opyt primenenija advantana v lechenii atopicheskogo dermatita u detej. Pediatrija. Zhurnal im. G.N. Speranskogo. 2000; 79 (5): 18 [Korotky N.G., Taganov A.V., Shimanovsky N.L. Experience of advantan usage in treatment of pediatric atopic dermatitis. Pediatria. Journal named after G.N. Speransky. 2000; 79 (5): 18 (in Russ.)].
  9. Torrelo A. Methylprednisolone aceponate for atopic dermatitis. Int J Dermatol. 2017; 56 (6): 691–7. DOI: 10.1111/ijd.13485
  10. Täuber U: Dermatocorticosteroids: Structure, activity, pharmacokinetics. Eur J Dermatol. 1994; 6: 3–13.
  11. Täuber U. Skin pharmacokinetics of a new topical glucocorticosteroid MPA; in Scott RC, Guy RH, Hadgraft J (eds): Prediction of Percutaneous Penetration. London, IBC Technical Services, 1990; pp. 37–48.
  12. Dermatological and Transdermal Formulations. Ed. by Kenneth A. Walters. 2002.
  13. Täuber U. Pharmacokinetics and ‘bioactivation’ of MPA. J Eur Acad Dermatol Venereol. 1994; 3 (Suppl. 1): S23–S31. DOI: 10.1111/j.1468-3083.1994.tb01060.x
  14. Chamlin S.L., Kao J., Frieden I.J. et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002; 47 (2): 198–208. DOI: 10.1067/mjd.2002.124617
  15. Szczepanowska J., Reich A., Szepietowski J.C. Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study. Pediatr Allergy Immunol. 2008; 19 (7): 614–8. DOI: 10.1111/j.1399-3038.2007.00706.x
  16. Peserico A., Städtler G., Sebastian M. et al. Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study. Br J Dermatol. 2008; 158 (4): 801–7. DOI: 10.1111/j.1365-2133.2008.08436.x
  17. Günther, C., Kecskes, A., Staks, T. et al. Percutaneous Absorption of Methylprednisolone Aceponate following Topical Application of Advantan® Lotion on Intact, Inflamed and Stripped Skin of Male Volunteers. Skin Pharmacol Physiol. 1998; 11 (1), 35–42. DOI: 10.1159/000029806
  18. Loden M, Maibach I (eds.). Treatment of Dry Skin Syndrome: The Art and Science of Moisturizers. Berlin: Springer, 2012.