1. 2012;15;E701-E710Tissue Distribution of Clonidine Following Intraforaminal Implantation of Biodegradable Pellets: Potential Alternative to Epidural Steroid for Radiculopathy
   Animal Study
   Timothy R. Deer, MD, Jared T. Wilsey, PhD, Andrew JL Walsh, PhD, Douglas P. Beall, MD, Julie H. Block, BS, William F. McKay, ME, and John M. Zanella, MS.

BACKGROUND: Epidural steroid injections have shown efficacy in short-term pain relief, but often require repeated injections in order to provide continued pain relief. It has been suggested that a continuous, locally administered dose of an anti-inflammatory compound may provide sustained pain relief at doses lower than those needed with injections.

OBJECTIVE: To evaluate the distribution of clonidine after transforaminal placement of a biodegradable drug delivery depot system.

STUDY DESIGN: A preclinical animal study.

METHODS: A biodegradable polymer drug depot designed to provide sustained delivery of clonidine was placed in or near a single lumbar neural foramen in 12 farm pigs.  Clonidine tissue concentrations were measured at the implant site and at incremental distances from the implant over a time period of 12 weeks. Plasma clonidine levels were measured at 4 hours postimplantation on days 1, 2, 3, 5, and 7, and then weekly until the termination of the study.

RESULTS: Clonidine was detectable up to 6 cm away from the drug depot. The highest concentrations of clonidine were present within the targeted spinal nerve; the concentration decreased with increasing distance from the depot. Clonidine was undetectable in plasma from all animals at all time points.

LIMITATIONS:  While clonidine was detected up to 6 cm from the drug depot, it is unknown if the drug concentration has clinical relevance. 

CONCLUSIONS: The results indicate that a biodegradable depot designed to be placed in a specific location to provide local sustained release of an anti-inflammatory and analgesic drug may be a feasible new approach to treat radicular pain associated with intervertebral disc pathology and other spinal conditions.