Long-Term Ocular Safety and Systemic Toxicokinetics of Doxycycline Hyclate Ophthalmic Solution: A 270-Day GLP Study in Juvenile Rabbits

Background: Pediatric myopia is highly prevalent in Asian populations and has been associated with scleral extracellular matrix remodeling. Doxycycline hyclate, a tetracy-cline-class compound with matrix metalloproteinase–inhibitory activity at sub-antimicrobial doses, is under investigation for long-term ophthalmic use. Methods: A GLP-compliant 9-month repeat-dose ocular toxicity study (Study No. 2098-005) was conducted in juvenile Dutch Belted rabbits. Animals received topical bilateral admin-istration of doxycycline hyclate ophthalmic solution (0.01%, 0.1%, or 0.5%) twice daily, followed by a recovery period. Evaluations included clinical and ophthalmic observa-tions, intraocular pressure, clinical pathology, toxicokinetics, and gross and microscopic pathology. Results: No treatment-related mortality or adverse clinical findings were observed. Body weight gain, ophthalmic examinations, intraocular pressure, and clinical pathology parameters showed no test article–related effects. Systemic exposure in-creased with increasing dose, with low accumulation following repeated administration and no apparent sex-related differences. No test article–related macroscopic or micro-scopic findings were identified. Conclusion: Long-term topical administration of doxycycline hyclate ophthalmic solution was well tolerated in juvenile rabbits, sup-porting its further clinical development for chronic ophthalmic indications.