Do local anesthetics have an influence on the percutaneous penetration of a model corticosteroid? An in vivo study using the vasoconstrictor assay.
Local anesthetics may exert nonspecific interactions with membrane components which can affect drug permeability. To investigate pharmacodynamically whether these membrane interactions lead to penetration enhancement of the coadministered model drug betamethasone-17-benzoate through human skin, the vasoconstrictor assay was used. Information on the penetration-enhancing properties of local anesthetic-containing vehicles compared to a plain standard were obtained from activity-response curves, where the enhancement factor was determined from the horizontal distance between the standard and a test in the linear range of the curves. The local anesthetics are able to enhance drug penetration through human skin to a different extent with lidocaine being the most efficient enhancer. An increase in the drug solubility and the diffusion coefficient in the stratum corneum due to membrane fluidization are possible mechanisms of action.
Römmen
C
C
Department of Pharmaceutical Technology, Heinrich-Heine-University, 40225, Düsseldorf, Germany.
Leopold
C S
CS
Lippold
B C
BC
D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005041:Etidocaine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009824:Ointments; D012867:Skin / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000779:Anesthetics, Local; D009824:Ointments; D013748:Tetracaine; D003907:Dexamethasone; D008012:Lidocaine; D005041:Etidocaine