In Vivo Elution Rate of Drug Eluting Ceramic Leads with a Reduced Dose of Dexamethasone Sodium Phosphate

Abstract

We have evaluated the in vivo elution rate and the threshold voltage performance of a new lead incorporating a controlled delivery device based on a porous ceramic collar. The drug, dexamethasone sodium phosphate (DSP less than 0.2 mg), was contained within the pores of a ceramic collar that was positioned externally and adjacent to a 4 mm2 Pt/Ir coated electrode. Thirty-three leads comprising a porous ceramic drug eluting collar (DEC) were implanted in the right ventricle of 12 sheep. In vivo elution was determined by analyzing the drug remaining in the collar after 1, 3, 11, and 28 days. Voltage thresholds were measured at implant and then weekly for 28 days on three sheep. Results were compared to leads with identical electrodes but with silicone DEC (DSP less than 0.5 mg). The in vivo elution rate of the ceramic DEC leads was fast with approximately 50% of the drug content on the first day. Although the drug content and elution rates were different for the ceramic and silicone DEC leads, the threshold performance of the leads was similar. For ceramic and silicone DEC leads, threshold voltages at implant and at 4 weeks were 0.29 +/- 0.09 compared to 0.37 +/- 0.08 and 0.42 +/- 0.08 compared to 0.44 +/- 0.13, respectively. The results show that a relatively rapid release of a reduced dose of DSP from a DEC is still effective in reducing threshold peaking.