May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
A Pharmacokinetic Model Describing Ocular And Systemic Disposition Of Ranibizumab In Rabbits
Author Affiliations & Notes
  • J. Gaudreault
    Clinical and Experimental Pharmacology,
    Genentech Inc, South San Francisco, CA
  • L.A. Damico
    Clinical and Experimental Pharmacology,
    Genentech Inc, South San Francisco, CA
  • P.C. Haughney
    Clinical and Experimental Pharmacology,
    Genentech Inc, South San Francisco, CA
  • M. Reich
    Clinical and Experimental Pharmacology,
    Genentech Inc, South San Francisco, CA
  • J. Rusit
    BioAnalytical Assays,
    Genentech Inc, South San Francisco, CA
  • B.B. Bender
    Clinical and Experimental Pharmacology,
    Genentech Inc, South San Francisco, CA
  • Footnotes
    Commercial Relationships  J. Gaudreault, Genentech E; L.A. Damico, Genentech E; P.C. Haughney, Genentech E; M. Reich, Genentech E; J. Rusit, Genentech E; B.B. Bender, Genentech E.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1854. doi:
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      J. Gaudreault, L.A. Damico, P.C. Haughney, M. Reich, J. Rusit, B.B. Bender; A Pharmacokinetic Model Describing Ocular And Systemic Disposition Of Ranibizumab In Rabbits . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1854.

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

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Abstract

Abstract: : Purpose: To develop a pharmacokinetic model describing ocular and systemic disposition of ranibizumab in New Zealand White (NZW) rabbits following several routes of administration. Methods:Studies were conducted in which >60 NZW rabbits were dosed with ranibizumab (500 or 625 µg/eye, 50 uL) directly into the vitreous body (ITV) or anterior chamber (AC). Animals were euthanized at timepoints ranging from 4 hours to 30 days, in order to collect the vitreous and aqueous humors, and retina tissue. Ranibizumab concentrations were measured in serum and each ocular matrix using ELISA. Five NZW rabbits were also dosed intravenously (IV) at 625 µg/animal with serial serum collections over 24 hours. Noncompartmental analyses were used to calculate half–lives (t1/2) and provide initial parameter estimates for a compartmental model, which was developed using non–linear least squares regression. Results: When administered IV, serum ranibizumab concentrations declined biexponentially with a mean ± sd terminal t1/2 of 3.05 ± 1.22 hours and a mean ± sd clearance of 42.8 ± 5.42 mL/hr/kg. After ITV administration, disposition in the vitreous humor appeared monoexponential, with a t1/2 of 3 days. After AC administration, disposition in the aqueous humor was biphasic, with an initial rapid decline in concentration and terminal t1/2 of 1 day. Using compartmental methods, the data are well described using a 5–compartment model. Conclusions: Intravitreal dosing provided the highest ranibizumab concentrations and longest t1/2 in the ocular compartments. Ranibizumab disposition from the 3 different dosing routes was well characterized by a 5–compartmental model; this model may prove useful in the development of alternative dosing regimens for ranibizumab.

Keywords: age–related macular degeneration • retina • pharmacology 
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