Effects of oral cyclosporine and cremophor-EL on microvascular dynamics and the barrier function of skin in the nude rat.

Studies were conducted to asses the impact of the oral administration of cyclosporine and cremophor-EL on parameters important to the per-cutaneous penetration of compounds through nude rat skin. The two parameters chosen were dermofluorometric response to injected fluorescein (reflecting vascularity and perfusion) and trans-epidermal water loss (reflecting barrier function). Differences were seen in the elimination phase of the dermofluormeter curves at 7 and 14 days. Some of these changes persisted in animals treated with cremophor-EL for 21 days but were not evident in the cyclosporine treated group. After cessation of treatment with other compound differences were again noted at 7 and 14 days. The change seen were thought to reflect vasodilatory responses consequent to cremophor-EL stimulated release of modulators superimposed on the nephrotoxic effects of cyclosporine. Trans-epidermal water loss consistently lowers from the flanks than from abdomen of animals regardless of treatment regimen with the exception of animals given cyclosporine for 7 days. At that time there was no significant difference between the flank and abdominal readings.