Abstract
Purpose :
Data for the ocular distribution of two drugs, triamcinolone acetonide (TA, corticosteroid) and CLS011A (tyrosine kinase inhibitor) following suprachoroidal administration in rabbit eyes, will be presented.
Methods :
Suprachoroidal and intravitreal administration of TA (40 mg/mL) was performed bilaterally into rabbit eyes. An additional group of animals were injected with a proprietary aqueous suspension of CLS011A (40 mg/mL) into the suprachoroidal space (SCS). Animals (n=2/time point) were sacrificed on at least 5 time points within 91 days. Ocular tissues (sclera/choroid/retinal pigment epithelium: SCR, retina, vitreous, iris-ciliary body: ICB, aqueous, and lens) and plasma were collected for quantification of drug concentrations. Analyses were performed using high performance liquid chromatography assays.
Results :
TA was detectable throughout the 91 day period in eyes dosed by either suprachoroidal or intravitreal administration. Based on area under the curve analysis, 96% of the drug was exposed to SCR and retina after SCS administration, in comparison to 20% in these tissues following intravitreal administration (IVT). Retinal exposure was similar between the two groups: 19% SCS vs 15% IVT. A large difference was seen in the ICB exposure: <1% SCS vs 25% IVT. Results from suprachoroidal CLS011A showed drug levels in the SCR that were at least 3 orders of magnitude higher than vitreous and drug was below limits of detection (1 ng/mL) in the aqueous. These relative distribution levels for each drug were maintained during the 3 month study period.
Conclusions :
Suprachoroidal administration of TA and CLS011A were targeted to the SCR and retina and targeting was maintained over 3 months. These data might have implications for a better therapeutic and/or safety profile for the treatment of chorio-retinal diseases.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.