Tissue distribution of clonidine following intraforaminal implantation of biodegradable pellets: potential alternative to epidural steroid for radiculopathy

Pain Physician. 2012 Sep-Oct;15(5):E701-10.

Abstract

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.

MeSH terms

  • Analgesics / administration & dosage*
  • Analgesics / pharmacokinetics*
  • Animals
  • Clonidine / administration & dosage*
  • Clonidine / pharmacokinetics*
  • Disease Models, Animal
  • Drug Delivery Systems
  • Epidural Space / drug effects
  • Female
  • In Vitro Techniques
  • Lumbosacral Region
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Radiculopathy / drug therapy*
  • Swine
  • Time Factors
  • Tissue Distribution / drug effects

Substances

  • Analgesics
  • Clonidine