Iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint

In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexameth asone occurs. This delivery system has recently been introduced into veteri nary medicine for the same purpose. However, the pharmacokinetic justificat ion for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clini cal practice, the present investigation compared injection and iontophoresi s of dexamethasone-phosphate into the equine tibiotarsal joint, also known as the tarsocrual joint. The tibiotarsal joints of seven horses were inject ed with 4 mL of 6 mg/mL dexamethasone-phosphate. With a similar drug concen tration 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, tibiotars al joint synovium was collected. Local venous blood samples were also colle cted from the iontophoretic and passive application sites for analysis of p lasma drug concentrations. Because of the potential for conversion of dexam ethasone-phosphate to dexamethasone, an extraction and analysis protocol wa s developed for both chemicals. The technique demonstrated a linear range o f detection (0.39-12 mug/mL) and a capability for measuring both chemicals in plasma and synovium. Conversion of dexamethasone-phosphate to dexamethas one occurred during synovial incubation (37 degreesC) and following freeze- thaw cycles. In contrast to the measurable synovial concentrations of dexam ethasone-phosphate (2.3 +/-0.96 mg/mL) and dexamethasone (0.27 +/-0.07 mg/m L) following injection, neither drug was detected in the synovium or the lo cal venous blood following iontophoretic or passive applications. In conclu sion, these results do not confirm iontophoretic or passive delivery of mea surable dexamethasone-phosphate into the tibiotarsal joint using current cl inical methods.