Measurement of pharmacodynamic effects of dexamethasone on epidermis by phosphorus nuclear magnetic resonance spectroscopy in vitro.
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. Phosphomonoesters 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.
Collier
S W
SW
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Sardón
S
S
Ruiz-Cabello
J
J
Johnson
W A
WA
Cohen
J S
JS
Schwartz
S L
SL
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004983:Ethanolamines / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000493:pharmacokinetics; D010758:Phosphorus / Q000378:metabolism; D010759:Phosphorus Isotopes; D013552:Swine; D013556:Swine, Miniature
D004983:Ethanolamines; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D010758:Phosphorus; D003907:Dexamethasone