Ketoprofen tissue permeation in swine following cathodic iontophoresis

Background and Purpose. Pharmacokinetic assessment of drug tissue permeatio n following iontophoresis is limited. The depth of ketoprofen tissue permea tion following cathodic iontophoresis (4 mA, 40 minutes) and the stereosele ctivity of drug delivery were examined in this study. Subjects. Ketoprofen (750 mg) was iontophoresed onto one porcine medial thigh, with passive drug permeation conducted on the other thigh. Methods. Skin, subcutaneous fasci a, and muscle biopsies from the drug delivery sites were harvested and stor ed separately, and the "R" and "S" ketoprofen enantiomers were determined. Results. Iontophoretic and passive applications yielded equivalent total ke toprofen concentrations in the skill and fascia. in contrast, multivariate analysis demonstrated that the ketoprofen concentration in the first centim eter of muscle following iontophoresis was greater than the drug concentrat ion in the deeper underlying muscle layers and greater than that delivered to any muscle layer following passive delivery. No transcutaneous stereosel ective delivery of ketoprofen was detected. Conclusion and Discussion. Comp ared with passive delivery, iontophoresis enhances nonstereoselective ketop rofen permeation into the fascia-muscle interface. With delivery to deeper tissue sites, however, there is no apparent enhancement over passive applic ation.