April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Evaluation of the Pharmacokinetics of Ketorolac Ophthalmic Solutions in Rabbit
Author Affiliations & Notes
  • M. Attar
    Pharmacokinetics and Drug Metabolism,
    Allergan, Irvine, California
  • R. M. Schiffman
    Gbl Prod Enhancement,
    Allergan, Irvine, California
  • L. Borbridge
    Bioanyl Sci,
    Allergan, Irvine, California
  • Q. Farnes
    Prod Formulation Dev,
    Allergan, Irvine, California
  • D. Welty
    Pharmacokinetics and Drug Metabolism,
    Allergan, Irvine, California
  • Footnotes
    Commercial Relationships  M. Attar, Allergan, Inc., E; R.M. Schiffman, Allergan, Inc., E; L. Borbridge, Allergan, Inc, E; Q. Farnes, Allergan, Inc., E; D. Welty, Allergan, Inc., E.
  • Footnotes
    Support  Allergan, Inc.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1989. doi:
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    • Get Citation

      M. Attar, R. M. Schiffman, L. Borbridge, Q. Farnes, D. Welty; Evaluation of the Pharmacokinetics of Ketorolac Ophthalmic Solutions in Rabbit. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1989.

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

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Abstract

Purpose: : Ketorolac ophthalmic solutions containing the preservative benzalkonium chloride are available for 4-times-daily administration (QID) as 0.4% and 0.5% aqueous solutions, pH = 7.4. This study evaluated the pharmacokinetics of a newly formulated, preservative-free 0.45% ketorolac solution, pH = 6.8, containing carboxymethylcellulose (CMC), developed to treat pain and inflammation following cataract surgery.

Methods: : Bilateral ocular instillations of ketorolac ophthalmic solutions were administered to rabbits. Aqueous humor and iris ciliary body tissues were extracted, and concentrations of ketorolac were determined using liquid chromatography-tandem mass spectrometry.

Results: : A novel CMC-based 0.45% ketorolac formulation increased ocular bioavailability by approximately 200% in aqueous humor and 300% in the iris-ciliary body relative to the 0.4% ketorolac formulation. In aqueous humor, the CMC-based 0.45% ketorolac formulation increased the maximum concentration (Cmax) from 211 to 389 ng/mL and area under the concentration time curve (AUC0-t) from 465 to 939 ng•hr/mL compared to the 0.4% ketorolac formulation. In iris-ciliary body, the CMC-containing 0.45% ketorolac solution increased Cmax from 216 to 450 ng/g and AUC0-t from 699 to 2040 ng•hr/g compared to the 0.4% ketorolac formulation. In pharmacokinetic simulations, twice daily (BID) administration of the CMC-based 0.45% ketorolac solution demonstrated higher ketorolac concentrations compared to QID administration with 0.4% ketorolac solution.

Conclusions: : A novel CMC-containing formulation of 0.45% ketorolac improved ocular delivery of active drug. This ketorolac formulation permits dosing of BID vs QID.

Keywords: wound healing • inflammation 
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