Microdialysis for the evaluation of penetration through the human skin barrier - a promising tool for future research?

The direct measurement of local drug concentration levels at discreet skin locations with minor trauma has recently become possible with the introduct ion of cutaneous microdialysis. Cutaneous microdialysis is an in vivo sampl ing technique for measuring solutes in the extracellular fluid of the dermi s. When used in combination with other experimental approaches, for example with a variety of non-invasive techniques to describe the functional statu s of the skin (bioengineering methods), it may help investigators to gain n ew insights into the fields of skin diseases, metabolism and drug absorptio n/penetration. An important parameter to describe the efficacy of microdial ysis is the relative recovery. This is the ratio between the concentration of a substance in the dialysate and the true extracellular concentration. S everal methods are in common use to describe the relative recovery (no-net- flux method or retrodialysis). Parameters such as probe design, depth of th e probe in the dermis, physico-chemical properties of the compound of inter est, and analytical aspects are important factors influencing microdialysis . Microdialysis has been used to investigate the influence of penetration e nhancers, vehicles or iontophoresis on percutaneous absorption, performed b y in vivo studies in rats. Tn human volunteers, most of the experiments hav e been performed to study the kinetics of fast penetrating substances, e.g. nicotine, non-steroidal antiinflammatory drugs, local anaesthetics, or sol vents. Problems have been encountered in the detection of lipophilic and hi ghly protein-bound substances. Further, dermal metabolism and the influence of barrier perturbation on percutaneous absorption have been analyzed, inv estigations suggest that microdialysis, in combination with traditional tec hniques, might give valuable information regarding the assessment of the pe netration of drugs and other exogenous agents through the skin. In spite of the clearly defined and accepted advantages of microdialysis technology fo r studies of transdermal drug delivery, to date no standardized test proced ure exists nor has the reproducibility of the results been evaluated, in th e future, these problems have to be solved to enable this method to find it s place in standard research. (C) 2001 Elsevier Science B.V. All rights res erved.