Purchase this article with an account.
J.-E. C. Lin, M. R. Robinson, S. M. Whitcup, B. D. Kuppermann, D. Welty; Pharmacokinetics Comparison of an Intravitreally Administered Biodegradable Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS Applicator System). Invest. Ophthalmol. Vis. Sci. 2007;48(13):5824.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To compare the vitreal and retinal pharmacokinetics of an intravitreally administered biodegradable drug delivery system designed to release 0.35 mg and 0.7 mg dexamethasone (DEX PS DDS, Allergan, Inc.) in rabbits and primates.
New Zealand White rabbits (n=6/ timepoint) and primates (n=3/ timepoint) were intravitreally injected unilaterally with 0.35 mg or 0.7 mg DEX PS DDS. Vitreous humor and retinal dexamethasone concentrations were monitored up to 6 months. Dexamethasone concentrations were quantified in rabbit and monkey samples using validated liquid chromatography/ mass spectroscopy.
The rabbit peak vitreoretinal dexamethasone concentration for 0.35 mg and 0.7 mg DEX PS DDS was dose-proportional. The rank order of dex concentration was retina > VH > AH indicating targeted delivery to posterior segment. An early (2-6 weeks) peak retinal dexamethasone concentrations, 5420 and 89900 ng/g, in the rabbit and monkey retina were observed. The peak dexamethasone concentrations (2-6 weeks) in VH distal to the implant were 3520 and 100 ng/mL in rabbit and primates, respectively. A dexamethasone concentration of 12.6 ng/mL was detected in the primate VH in close proximity to the implant at 6 months.
The in vivo pharmacokinetic release profile resulted in high vitreoretinal pulse concentration of dexamethasone with detectable low concentration in the vitreous up to 6 months. This is consistent with a release profile delivering pulse corticosteroid kinetics in clinical diseases or other inflammatory disease.
This PDF is available to Subscribers Only