We postulate that for future somatostatin therapies to treat posterior segment ocular diseases effectively, administration regimens must ensure that optimal drug levels are reached at the target ocular somatostatin receptors. A new class of non-peptide imidazolidinedione somatostatin agonist (NISA) drugs has demonstrated ocular anti-neovascular pharmacological activity and offers advantages to somatostatin peptide analogs which are less suited to penetrating ocular tissue barriers. We propose to study the pharmacokinetics and distribution of a prototype NISA compound in ocular tissues. The distribution of the compound will be studied first in the retinal and vitreous compartments of the rat after intravitreal vs. systemic administration. The results will guide more precise ocular pharmacokinetic studies on the compound in rabbits. Secondly, we will measure drug levels after the peribulbar transcleral ocular delivery in rabbits in vivo. Finally, the ocular permeability will be investigated using an established in vitro model. This will serve as the basis for more extensive in vitro and in vivo testing program for NISA analysis. ? ? ? ?
| Palii, Stela S; Afzal, Aqeela; Shaw, Lynn C et al. (2008) Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor. Invest Ophthalmol Vis Sci 49:5094-102 |
