ESTIMATION OF A CONCENTRATION PROFILE OF ACYCLOVIR IN THE SKIN AFTER TOPICAL ADMINISTRATION

The Laplace transformed equations for the time courses of drug concentration in the skin and net absorption were derived from Fick's diffusion law assuming a two-layer skin model. Based on these equations, a new method for estimating drug concentration in the skin directly from the absorption profile was developed by the use of a fast inverse Laplace transform (FILT) algorithm. The absorption profiles of topically administered acyclovir in rats obtained through deconvolution of urinary excretion time courses against i.v. injection data were analyzed according to this method. The amount of acyclovir excreted into urine was only 0.42% of the applied dose at 8 h after topical application with polyethylene glycol ointment, suggesting low skin permeability, while most of acyclovir injected intravenously was excreted within 4 h. However, the analysis revealed that a considerable level (57 mug/cm3) higher than the minimum inhibitory concentration (MIC) was maintained in the viable tissue under the steady-state conditions.