Superior nuclear receptor selectivity and therapeutic index of methylprednisolone aceponate versus mometasone furoate.
Although introduced more than 50 years ago, topical glucocorticoids are still the first line therapy for many inflammatory skin disorders such as atopic eczema, contact dermatitis and many others. Recently, significant improvements have been made to optimize the ratio of desired to unwanted effects. While with early compounds such as triamcinolone, topical side effects such as skin atrophy and telangiectasias can be observed rather frequently, newer drugs such as methylprednisolone aceponate or mometasone furoate have a significantly improved therapeutic index. The present study compared these two modern topical glucocorticoids, which possess the highest therapeutic index currently found, in terms of nuclear receptor selectivity in vitro and induction of the most important local side effects (skin atrophy and telangiectasias) in a relevant rodent model in vivo. We demonstrate that methylprednisolone aceponate displays higher specificity in nuclear receptor binding compared with mometasone furoate. Methylprednisolone aceponate was also markedly superior in terms of minimizing induction of skin atrophy or telangiectasias when compared with mometasone furoate. Based on these observations, methylprednisolone aceponate is expected to have a greater therapeutic index as compared with mometasone furoate, at least in the test systems used here. The degree to which this observation may translate into a clinical setting requires confirmation.
Mirshahpanah
Parham
P
Research Business Area Dermatology, Berlex Biosciences, Richmond, CA, USA.
Döcke
Wolf-Dietrich
WD
Merbold
Udo
U
Asadullah
Khusru
K
Röse
Lars
L
Schäcke
Heike
H
Zollner
Thomas M
TM
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D011923:Rats, Nude; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000473:pathology; D013684:Telangiectasis / Q000139:chemically induced / Q000473:pathology
D000893:Anti-Inflammatory Agents; D011244:Pregnadienediols; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D018161:Receptors, Mineralocorticoid; D011980:Receptors, Progesterone; D000068656:Mometasone Furoate; C078007:methylprednisolone aceponate; D008775:Methylprednisolone