Evaluation of skin penetration of topically applied drugs in humans by cutaneous microdialysis: acyclovir vs. salicylic acid

Abstract

Background and objective: Cutaneous drug application is used for both local drug therapy and systemic treatment. For both types of treatment, the drug concentration profile in, and transport across, the skin is important. To evaluate skin penetration of topically-applied drugs we recently used cutaneous microdialysis. The aim of this study was the use of this method for studying acyclovir and salicylic acid. Method: Five per cent acyclovir cream was applied on intact and tape-stripped skin of healthy volunteers and 5% salicylic acid ointmentonto intact skin of other volunteers. Microdialysis probes with 2 kDa molecular weight cut-off were inserted intradermally and were perfused with Ringer solution. Drug concentrations were measured by high-performance liquid chromatography. Results: Following topical application of 5% acyclovir cream onto intact skin of eight healthy volunteers, no drug was determinable in the skin (cutaneous microdialysate) in any of the subjects studied. After partial removal of the stratum corneum the penetration of this drug into skin increased markedly. The mean maximum skin concentration was about 2AE5 lmol/L after 2AE4 ± 0AE7 h. Topically applied salicylic acid penetrated intact skin with a maximum concentration in the cutaneous microdialysate of 7AE57 ± 3AE90 lmol/L after 5AE3 ± 0AE4 h.Conclusion: Cutaneous microdialysis is a valuable method for estimating skin concentration of topically-applied drug. It allows evaluation after application to a small skin area, of about 2 cm 2 , thereby reducing the risk of systemic toxicity. The method may be helpful for evaluating the influence of skin condition on the transport process.

The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues

“…The advantage of such route can be partly due to the avoidance of first-pass metabolism. However, only a fraction of the drug applied to the skin surface reaches the systemic blood circulation and this amount will not necessarily reflect the concentration in the target organ (Klimowicz et al 2007). …”

“…Several experimental methods have been elaborated for this purpose, for instance, skin blister fluid and microdialysis, particularly in the skin which is described in papers of Holmgaard (2010), Klimowicz (2007) and Olczyk (2008). Apart from these two methods, using labeled compounds is one of the techniques frequently applied to estimate drug penetration into the skin and other body tissue or organs (Bielecka-Grzela et al 2002).…”

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

“…Based on older studies in atopic patients, an increase in the penetration of exogenous compounds is then expected [126] . In a number of in vivo DMD studies, the impact of experimentally induced skin barrier perturbation on the cutaneous penetration of different substances has been demonstrated [12,42,50,78,127] . Benfeldt et al [12] have studied the effect of different barrier disruption methods on cutaneous penetration in humans ( fig.…”

“…Other recent studies have compared e.g. the penetration of acyclovir and salicylic acid on disrupted skin barriers using DMD and tape stripping [78] , and the penetration of a metronidazole cream formulation (1%) applied to the forearm skin in areas of both irritant dermatitis and nor- mal skin [42,103] . These studies demonstrated increased drug penetration in barrier-disrupted skin as well as the usefulness of the MD methodology for drug penetration studies.…”

Application of Dermal Microdialysis for the Determination of Bioavailability of Clobetasol Propionate Applied to the Skin of Human Subjects

“…It has been successfully used to investigate endogenous substances in extracellular fluid in the skin [3,4] and for studies of the absorption of exogenous substances as well [5][6][7] . The MD technique can be used to assess the permeation of topically applied drugs across both healthy and diseased or perturbed skin [8][9][10] . More recently, it has been shown to be a useful technique to assess bioequivalence of some topical formulations [11][12][13][14] .…”