Acyclovir concentrations in the skin of humans after a single oral dose assessed by in vivo cutaneous microdialysis.

Background/purpose: Acyclovir is a synthetic deoxyguanosine analogue used in the treatment of certain viral diseases. This drug is effective primarily against Herpes simplex virus, Varicella zoster virus and to a lesser extent against Epstein-Barr virus and cytomegalovirus. The aim of the study was to determine the acyclovir concentrations in plasma and skin (cutaneous microdialysate) and to compare its penetration into real (skin) and theoretical peripheral compartment after administration of a single 0.4 g oral dose.

Methods: To evaluate the skin concentrations of the examined agent in 10 healthy male volunteers linear microdialysis probes with 2 kDa molecular-weight cut-off were inserted intradermally and were perfused with Ringer solution up to 6 h after drug ingestion.

Results: The mean maximum acyclovir concentrations in the plasma, skin and theoretical peripheral compartment were 3.16+/-0.86, 0.94+/-0.34 and 1.85+/-0.69 micromol/L, respectively, and were achieved after 1.6+/-0.4, 2.4+/-0.3 and 3.7+/-0.7 h. The degree of penetration into the real (skin) and theoretical peripheral compartment was 0.36+/-0.15 and 0.74+/-0.12, respectively, and the differences were statistically significant. Similarly, also, the maximum concentration, time to maximum concentration and area under the concentration-time curve differed significantly between the plasma and skin as well as between the skin and the theoretical peripheral compartment.

Conclusions: In selected cases skin concentrations should be determined rather than those in blood plasma when studying the distribution of orally administered drugs. Evaluation of acyclovir concentrations in the skin cannot be replaced by the calculation of the theoretical peripheral compartment.