Ketoprofen Tissue Permeation in Swine Following Cathodic Iontophoresis

Abstract

Background and Purpose. Pharmacokinetic assessment of drug tissue permeation following iontophoresis is limited. The depth of ketoprofen tissue permeation following cathodic iontophoresis (4 mA, 40 minutes) and the stereoselectivity 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 fascia, and muscle biopsies from the drug delivery sites were harvested and stored separately, and the “R” and “S” ketoprofen enantiomers were determined.Results. Iontophoretic and passive applications yielded equivalent total ketoprofen concentrations in the skin and fascia. In contrast, multivariate analysis demonstrated that the ketoprofen concentration in the first centimeter of muscle following iontophoresis was greater than the drug concentration in the deeper underlying muscle layers and greater than that delivered to any muscle layer following passive delivery. No transcutaneous stereoselective delivery of ketoprofen was detected.Conclusion and Discussion. Compared with passive delivery, iontophoresis enhances nonstereoselective ketoprofen permeation into the fascia-muscle interface. With delivery to deeper tissue sites, however, there is no apparent enhancement over passive application.

Cathodic iontophoresis of ketoprofen over the equine middle carpal joint

“…In comparison to the passive application, cathodic iontophoresis enhanced ketoprofen delivery at only the first cm of muscle, but did not enhance ketoprofen delivery in the other tissues analysed. The lack of detectable ketoprofen in the systemic vasculature in the present equine model was similar to our previous ketoprofen results in both man (Panus et al 1996 and swine (Panus et al , 1999. Finally, the absence of measurable ketoprofen in the synovium in the present iontophoretic investigation parallels our previous dexamethsone-phosphate iontophoretic results (Blackford et al 2000).…”

“…The present investigation is the first to examine cathodic iontophoresis of ketoprofen in a compartment this deep in any animal model. Our previous research with cathodic iontophoresis of ketoprofen resulted in measurable concentrations in both man (Panus et al 1996 and swine (Panus et al , 1999. However, in these previous investigations the ketoprofen was measured in more superficial tissues.…”

“…In man, cathodic iontophoresis delivered pharmacologically relevant concentrations of ketoprofen to the superficial local venous blood (Panus et al 1996, a proxy for transcutaneous delivery of ketoprofen ( Tashiro et al 2000). In swine, iontophoresis delivered significantly more ketoprofen to the fascia-muscle interface than did passive delivery (Panus et al , 1999. Transcutaneous ketoprofen delivery has also been demonstrated following passive application (Baixauli et al 1990;Shah et al 1996), and one investigation documented passive drug delivery into the synovial space of the human knee (Ballerini et al 1986).…”

Iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint

“…In the present investigation, dexamethasone-phosphate and dexamethasone in local venous blood proximal to the application site were utilized as markers of iontophoretic drug delivery to subcutaneous and muscular tissues with access to the vasculature. Our previous research demonstrated that cathodic iontophoresis (4 mA, 40 min, 0.28 mA/cm 2 ) of ketoprofen (300 mg/mL) resulted in transcutaneous permeation of the drug into the subcutaneous fascia and muscle in the pig (Panus et al, 1999). Iontophoresis of ketoprofen under similar conditions onto the human forearm also resulted in approximately 1 mg/mL of the drug in the local venous blood at the termination of iontophoresis (Panus et al, 1996.…”

“…Several pharmacokinetic parameters involved with the iontophoresis of ketoprofen, a NSAID, have been documented. Utilizing iontophoretic parameters from clinical practice, cathodic iontophoresis enhanced ketoprofen tissue permeation down to the fascia-superficial muscle interface (Panus et al, 1999). Using the same iontophoretic parameters, ketoprofen iontophoresis at the volar surface of the human wrist resulted in clinically relevant concentrations in the local venous blood when sampled at the ipsilateral antecubital fossa (Panus et al, 1996.…”