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

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 ointment-onto 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 2 x 5 micromol/L after 2 x 4 +/- 0 x 7 h. Topically applied salicylic acid penetrated intact skin with a maximum concentration in the cutaneous microdialysate of 7 x 57 +/- 3 x 90 micromol/L after 5 x 3 +/- 0 x 4 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.