Measurement of Pharmacodynamic Effects of Dexamethasone on Epidermis by Phosphorus Nuclear Magnetic Resonance Spectroscopy in Vitro

Autor: S.W. Collier, S.L. Schwartz, Jack S. Cohen, Jesús Ruiz-Cabello, W.A. Johnson, S. Sardón
Rok vydání: 1994
Předmět:
Zdroj: Journal of Pharmaceutical Sciences. 83:1339-1344
ISSN: 0022-3549
DOI: 10.1002/jps.2600830927
Popis: An intact, viable epidermal preparation was perfused and phosphoenergetic and phospholipid metabolite levels were measured by 31P NMR. The preparation was stable in the NMR perfusion apparatus for 24 h. The effects of inclusion of ethanolamine and dexamethasone-21-acetate in the perfusion media on phosphorus-containing metabolites was assessed by examination of serial 31P NMR spectra. Phospho-monoesters increased significantly during the fourth hour of perfusion with ethanolamine (3 mM) and remained elevated. A corresponding decrease in nucleotide triphosphates was noted, but phosphocreatine (PCr) remained unchanged. Dexamethasone perfusion resulted in a biphasic effect on phosphomonoester metabolism and a dose-dependent decrease in PCr and nucleotide triphosphate levels. A log-linear relationship was observed between dexamethasone dose in the 1–100-nM range and a decrease in PCr. These techniques with an isolated intact epidermal preparation are useful for elucidating mechanisms of corticosteroid action on the skin and serve as a basis for developing a mechanistically relevant topical corticosteroid bioequivalence technique.
Databáze: OpenAIRE