Effects of vasoconstriction on dermal pharmacokinetics and local tissue distribution of compounds.

The effects of the local vasoconstrictor phenylephrine on the dermal absorption kinetics and local tissue distribution of compounds were investigated in rats. Phenylephrine (0.0025% -0.1%) and tracer quantities of salicylic acid, lidocaine, and water were applied in an aqueous solution to the exposed rat dermis. The disappearance of salicylic acid from the solution into the rat dermis and its appearance in blood, local underlying tissues, and similar tissues on the contralateral side was quantified. The clearance of salicylic acid into the dermis decreased and the concentrations of salicylic acid in underlying tissues increased with an increase in phenylephrine concentration (up to 0.01%). The concentrations of salicylic acid in plasma and contralateral issues decreased with increasing phenylephrine concentrations. At higher phenylephrine concentrations, no significant increase in local tissue concentrations of salicylic acid was observed. The effects of phenylephrine on local tissue levels of lidocaine and tritiated water paralleled those found for salicylic acid. The concentration-depth profiles for solutes in underlying tissues with variable blood flows were described by a compartment-in-series pharmacokinetic model in which each tissue's blood flows to and from a central compartment were incorporated. The values predicted under varying degrees of vasoconstriction were found to compare well with the experimentally determined concentrations of salicylic acid, lidocaine, and water in issues below a dermal application site, in the presence of phenylephrine. Phenylephrine can significantly increase quantities of solutes delivered to local tissues after dermal application, the observed effects being due to the vasoconstrictive properties of phenylephrine. Blood flow changes in skin can have profound effects on dermal pharmacokinetics and relative processes of local and systemic solute distribution.