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


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Abstract

Methylprednisolone aceponate (MPA) is the latest glucocorticosteroid molecule developed for topical use, having advantageous ratio of safety and efficacy. Peculiarity of MPA is its 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 its equivalence to the original product is unknown. In the frames of this research the detection of MPA and its 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.

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About the authors

M. S Nesterov

Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia

D. V Khvostov

V.M. Gorbatov Federal Scientific Center for Food Systems Russian Academy of Sciences

R. A Ageldinov

Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia

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