PHARMACODYNAMIC MEASUREMENTS OF 8-METHOXYPSORALEN IN HUMAN SKIN

The efficiency of the epicutaneous microcirculation is important to th e elicitation of pharmacological effects and percutaneous absorption o f drugs. Laser Doppler flowmeter, chromameter and measurement of trans epidermal water loss (TEWL) were used to assess the extent of skin blo od flow, water loss and light absorption induced after topical adminis tration of 8-methoxypsoralen (8-MOP). TEWL monitors barrier function d irectly, while the chromameter measures the light reflected by the ski n. Irrespective of the concentration of 8-MOP applied, there is a good correlation between chromameter and evaporimeter readings. However, d ifferent drug concentrations elicited significant differences between laser Doppler flowmetry (LDF) and TEWL readings. The response measured with LDF was faster and greater when compared with the other measurem ents, suggesting that 8-MOP caused a rapid and intense response in ski n blood flow. Superficial responses, such as those produced by light r eflectance (chromameter) and transepidermal perturbations, were weaker following topical application of 8-MOP combined with UV irradiation ( PUVA). This information may be important in delineating guidelines for the clinical practice and instrumental monitoring of topical 8-MOP. T hese observations suggest that LDF provides a useful, noninvasive phys ical technique to monitor skin after PUVA. However, caution should be exercised in the interpretation of physical measurements for evaluatin g the degree of the clinical vasoresponse produced by PUVA treatment.