Quantification of Uptake and Clearance of Acyclovir in Skin Layers

Abstract

Background

Quantification of drug uptake and clearance in the skin layers could provide better insight into the skin kinetics of dermatological formulations aimed for deeper skin tissues. This study assessed the skin kinetics of acyclovir in different skin layers following topical application on the abdominal region of Wistar rats.

Methods

In vivo skin pharmacokinetics parameters were determined by two different protocols such as post drug load assessment and subsequent drug load assessment following topical application of 500 mg of cream formulation containing 5% (w/w) of acyclovir.

Results

Topical application of acyclovir exhibited concentration gradient between the skin layers (stratum corneum > viable epidermis > dermis) which were inconsistent over the time-course of the study. The rate and extent of drug reaching target site (basal epidermis) was relatively low. The drug uptake and clearance pro-files were found to be distinct in all the three skin layers suggesting no drug concentration correlation (P<0.05) between skin layers. Drug concentration in the viable epidermis continued to increase even after termination of therapy (T_max=4 h) and then declined rapidly. The availability of acyclovir in the target was comparatively low (approximately 0.4% of the applied dose) although an order of magnitude higher percentage was determined in the stratum corneum.

Conclusions

The data observed in this study demonstrates low skin uptake and rapid clearance of acyclovir in the target site. Further, the methodology employed can be useful for studying other topical antiviral agents as well as for optimizing formulations for drugs (such as acyclovir) that may enhance their efficacy.