September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Novel modeling for the Enhancement of Decision-Making Worthiness of Ocular Pharmacokinetic Study Results
Author Affiliations & Notes
  • Muhammad Abdulrazik
    East Jerusalem Biomedical Institute, East Jerusalem,
  • Footnotes
    Commercial Relationships   Muhammad Abdulrazik, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4005. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Muhammad Abdulrazik; Novel modeling for the Enhancement of Decision-Making Worthiness of Ocular Pharmacokinetic Study Results. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4005.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Enhancing the credibility of decisions based on ocular pharmacokinetic (PK) study results.

Methods : In two PK studies a single dose, of brimonidine tartrate (0.2%) or dexamethasone base (0.1 %), was instilled in the cul-de-sac of one eye of an albino rabbit. The whole-tissue-weight (WTW [gr]) was measured and drug concentrations were determined (at 15, 30 and 60 min. post instillation) for each of conjunctiva, cornea, sclera, ciliary-body, iris, choroid, aqueous-humor, lens, vitreous and retina. Fraction-of-administered-dose (FOAD [%]) was calculated from the administered dose (AD [ng]), drug concentration (C [ng/gr]) and WTW (FOAD=100.C.WTW/AD). Area-under-the-curve (AUC, 0-60 min. [ng.min/gr]) for each tissue is presented as % of the sum of AUC's for all tissues. Cubes-under-the-curve (CUC [ng.min]) is introduced as a per-whole-tissue PK parameter (CUC=AUC.WTW), in contrast to the per-gram AUC.

Results : Brimonidine retention in all ten tissues scored only 3.8±1.02% FOAD. The conjunctival stake, out of this, was 65.74±4.52% (FOAD), 66.18±2.68% (CUC) and 37.84±4.03% (AUC). Inside the non-conjunctival tissues stake: cornea and sclera, 42.81±7.59% (FOAD), 40.30±6.51% (CUC) and 42.79±2.97% (AUC); uveal tract tissues, 34.27±3.91% (FOAD), 35.68±3.18% (CUC) and 44.13±1.56% (AUC); aqueous humor, 11.16±3.89% (FOAD), 12.53±3.24% (CUC) and 7.7±1.61% (AUC); lens and vitreous, 8.63±0.75% (FOAD), 8.47±0.17% (CUC) and 1.63±0.11% (AUC); retina, 3.13±0.46% (FOAD), 3.03±0.11% (CUC) and 3.75±0.21% (AUC). In dexamethasone treated eye, the ten tissues, altogether, scored 4.04±0.56% FOAD. The conjunctival stake, out of this, was 67.85±2.41% (FOAD), 67.71±1.49% (CUC) and 37.34±1.16% (AUC). Inside non-conjunctival tissues stake: cornea and sclera, 62.05±8.37% (FOAD), 65.02±7.04% (CUC) and 69.25±5.78% (AUC); uveal tract tissues, 21.43±5.76% (FOAD), 19.41±4.84% (CUC) and 21.99±5.11% (AUC); aqueous humor, 6.63±1.65% (FOAD), 6.04±1.28% (CUC) and 3.42±0.66% (AUC); lens and vitreous, 6.01±1.09% (FOAD), 5.62±0.91% (CUC) and 0.90±0.07% (AUC); retina, 3.89±0.23% (FOAD), 3.91±0.07% (CUC) and 4.44±0.07% (AUC).

Conclusions : Ocular tissues are at diverse range of WTW. The AUC, inherently, underestimates drug retention at tissues with relatively high WTW, like the conjunctiva. Both FOAD and CUC, being WTW based, promise a significant enhancement to the credibility of decisions based on ocular pharmacokinetic study results.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×