June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Determination of in vitro-in vivo correlations of intraocular Kenalog half life with the PK-Eye posterior segment pharmacokinetic model
Author Affiliations & Notes
  • Sahar Awwad
    Pharmaceutics, The School of Pharmacy, UCL, London, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Steve Brocchini
    Pharmaceutics, The School of Pharmacy, UCL, London, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Peng Tee Khaw
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships Sahar Awwad, None; Steve Brocchini, None; Peng Khaw, University College London, Moorfields (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5725. doi:
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    • Get Citation

      Sahar Awwad, Steve Brocchini, Peng Tee Khaw; Determination of in vitro-in vivo correlations of intraocular Kenalog half life with the PK-Eye posterior segment pharmacokinetic model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5725.

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

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Abstract

Purpose: We have developed an in vitro ocular flow model (PK-Eye) to study the clearance pharmacokinetics of protein therapeutics and poorly soluble drugs and implants during preclinical studies. The use of our model is important to determine in vitro-in vivo correlations (IVIVC) and to optimise ocular pharmacokinetics. Steroid implants are increasingly being used clinically, however triamcinolone acetonide (TA, Kenalog®) has long been administered intravitreally. The PK-Eye has been utilized to determine IVIVC of TA.

Methods: The PK-Eye has an anterior and posterior cavity with an inlet port that allows phosphate buffered saline (PBS, pH 7.4) to flow at a fixed flow rate of 2.0 μL/min. Models were immersed in a pre-heated oil bath at 37°C. The kinetics of TA dissolution and clearance from the posterior cavity were determined with both PBS and simulated vitreous (polymeric combination of hyaluronic acid, HA and agar). TA (4.0 mg, 100 μL) was injected in the posterior cavity and samples were obtained from the anterior outflow sampling port. Samples were analysed by HPLC (254 nm) to determine clearance kinetics.

Results: TA displayed similar clearance times from PBS and simulated vitreous (26.1 ±0.8 and 27.8 ± 3.4 days respectively). Clearance was solubility limited and followed a linear profile, which was 18.6 days in a non-vitrectomised eye after the same dose (4mg) in humans.(Beer PM et al 2003)<br />

Conclusions: The IVIVC for TA was established. As a permeable molecule that is also capable of clearing by the retinal-choroid-scleral (RCS) pathway it may be possible to estimate the relative proportion of dose that cleared by the RCS as well as by aqueous outflow. In contrast, previous studies using antibodies which use this pathway much less showed much closed correlation of half life pharmacokinetics.

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