May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Pharmacokinetics Comparison of an Intravitreally Administered Biodegradable Dexamethasone Posterior Segment Drug Delivery System (DEX PS DDS Applicator System)
Author Affiliations & Notes
  • J.-E. C. Lin
    Allergan Inc, Irvine, California
    Pharmacokinetic & Drug Metab,
  • M. R. Robinson
    Allergan Inc, Irvine, California
    Ophthalmology Clinical Research,
  • S. M. Whitcup
    Allergan Inc, Irvine, California
    Ophthalmology Clinical Research,
  • B. D. Kuppermann
    Department of Ophthalmology, School of Medicine, University of California, Irvine, California
  • D. Welty
    Allergan Inc, Irvine, California
    Pharmacokinetic & Drug Metab,
  • Footnotes
    Commercial Relationships J.C. Lin, Allergan, Inc., E; M.R. Robinson, Allergan, Inc, E; S.M. Whitcup, Allergan, Inc, E; B.D. Kuppermann, Allergan, Inc., C; D. Welty, Allergan, Inc, E.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5824. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: edema 
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