A time correlation study between reflectance spectroscopic cutaneous vasoconstriction and plasma corticosteroid concentration

Summary Although cutaneous vasoconstriction assays are used as a primary screen for ranking the in vivo efficacy of new corticosteroids and in vivo human drug delivery studies, little is known about the relationship between the blanching reaction and corticosteroid tissue or plasma concentrations. We measured cutaneous vascular reactions in five volunteers, using an improved reflectance spectroscopic method, and a sensitive radioimmunoassay technique was employed to measure plasma betamethasone concentrations. Using a specially developed betamethasone‐17‐valerate patch prepared in BIO‐PSA®, constant corticosteroid release was ensured, and correlations between cutaneous blanching and plasma corticosteroid concentrations were calculated. Maximal skin blanching was documented 12 h post‐application, whereas plasma corticosteroid concentrations peaked later, at 32 h post‐application, when a paradoxical telangiectatic vasodilatation occurred. At 72 h post‐application, when the plasma corticosteroid concentration was still above the 12 h level, this paradoxical vasodilatation was maximal. The corticosteroid‐induced vascular reactions were mainly due to arterial haemoglobin (Oxy Haem), and both vasoconstriction and vasodilatation were related to changes in Oxy Haem. Our results suggest a dual, probably both time and concentration related, interaction between corticosteroids and dermal vessels in which lower concentrations at 6‐12 h exposure caused vasoconstriction, but as the exposure time increased (24 h) paradoxical vasodilatation was induced, although plasma corticosteroid concentrations were still rising.