The potential of vasoconstrictors to enhance eye disease treatments in passive trans-scleral drug delivery was demonstrated. The higher DexP level in the eye and the improvement of the outcome in the efficacy study in the presence of the vasoconstrictor are consistent with the hypothesis that the vasoconstrictor enhances drug delivery by decreasing clearance.

No abstract

Phenylketonuria is an autosomal recessive disorder characterized by elevated concentrations of phenylalanine. Elevated phenylalanine concentrations can impair intellectual functions and the disease is treated with a lifelong diet and frequent monitoring of plasma phenylalanine concentrations. Previous in vitro studies have demonstrated the feasibility of iontophoretically enhanced transdermal transport of phenylalanine. Here we evaluate the feasibility of transdermal iontophoretic extraction of phenylalanine in vivo. Phenylalanine was iontophoretically extracted from the skin of healthy volunteers and of patients with phenylketonuria for up to 6 h and concentrations were compared with those measured in plasma. The amount of phenylalanine iontophoretically extracted from the skin declined over time, suggesting contribution of phenylalanine from the skin in the initial extraction. Phenylalanine iontophoretically extracted from skin correlated with plasma phenylalanine levels at plasma levels above 300 micromol/L. This correlation supports the feasibility of iontophoretic phenylalanine extraction for monitoring phenylketonuria.

Previous studies have demonstrated the ability of AC iontophoresis to control skin resistance in different transdermal iontophoresis applications. The objectives of the present study were to (a) identify the alternating current (AC) frequency for the optimization of AC pore induction of human epidermal membrane (HEM) and (b) determine the effects of chemical permeation enhancers upon the extent of pore induction under AC conditions. Experiments with a synthetic membrane system were first conducted as the control. In these synthetic membrane experiments, the electrical resistance of the membrane remained essentially constant, suggesting constant electromobility of the background electrolyte ions under the AC conditions studied. In the HEM experiments, the electrical resistance data showed that higher applied voltages were required to induce the same extent of pore induction in HEM at AC frequency of 1 kHz compared with those at 30 Hz. Even higher voltages were needed at AC frequencies of 10 kHz and higher. AC frequency also influenced the recovery of HEM electrical resistance after AC iontophoresis application. An optimal AC frequency region for effective pore induction and least sensation was proposed. Permeation enhancers were shown to enhance pore induction in HEM during AC iontophoresis. The enhancers reversibly reduced the AC voltage required to sustain a constant state of pore induction in HEM during AC iontophoresis, consistent with the mechanism of lipid lamellae electroporation in the stratum corneum.