Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs.

INTRODUCTION

The purpose of the present study was to examine the potential ocular and systemic toxicity and toxicokinetics/pharmacokinetics of sustained-release dexamethasone in canines.

METHODS

In this non-randomized study, intracanalicular depots (dexamethasone-loaded or placebo vehicle) were inserted into both eyes of 33 beagles. Tear fluid and plasma were collected for toxicokinetic/pharmacokinetic analysis of dexamethasone, ophthalmic examinations were performed for signs of toxicity, and urine and blood samples were collected for urinalysis, hematology, clinical chemistry, and coagulation analysis. Animals were observed daily for signs of toxicity. Macroscopic and microscopic evaluations were performed.

RESULTS

Mean dexamethasone tear fluid concentration from the dexamethasone group decreased from 4245 ng/mL 6-h post-insertion to 1044 ng/mL on Day 35. All plasma dexamethasone levels were below the limit of quantitation. No systemic or ocular toxicities were attributed to the dexamethasone depot.

CONCLUSION

Sustained-release dexamethasone produced no identifiable ocular or systemic toxicity in this animal model, and pharmacokinetics demonstrated a tapered, sustained drug release.

FUNDING

Ocular Therapeutix.