Iontophoresis of Dexamethasone-Phosphate Into the Equine Tibiotarsal Joint

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In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known as the tarsocrual joint. The tibiotarsal joints of seven horses were injected with 4 mL of 6 mg/mL dexamethasone-phosphate. With a similar drug concentration and over the same application site, six different horses underwent simultaneous cathodic iontophoresis (4 mA, 40 min) or passive application (0 mA, 40 min) on contralateral limbs. Following all applications, tibiotarsal joint synovium was collected. Local venous blood samples were also collected from the iontophoretic and passive application sites for analysis of plasma drug concentrations. Because of the potential for conversion of dexamethasone-phosphate to dexamethasone, an extraction and analysis protocol was developed for both chemicals. The technique demonstrated a linear range of detection (0.39-12 μg/mL) and a capability for measuring both chemicals in plasma and synovium. Conversion of dexamethasone-phosphate to dexamethasone occurred during synovial incubation (37 °C) and following freeze-thaw cycles. In contrast to the measurable synovial concentrations of dexamethasone-phosphate (2.3±0.96 mg/mL) and dexamethasone (0.27±0.07 mg/mL) following injection, neither drug was detected in the synovium or the local venous blood following iontophoretic or passive applications. In conclusion, these results do not confirm iontophoretic or passive delivery of measurable dexamethasone-phosphate into the tibiotarsal joint using current clinical methods.