Alternative Drug Delivery for Patients Undergoing Cataract Surgery as Demonstrated in a Canine Model

J Ocul Pharmacol Ther. Jan/Feb 2018;34(1-2):154-160. doi: 10.1089/jop.2017.0048. Epub 2017 Dec 11.

Abstract

Purpose: (1) To determine ketorolac concentrations in selected ocular tissues following the intracameral administration of phenylephrine and ketorolac injection 1%/0.3% (OMIDRIA®) delivered in irrigation solution during lens replacement surgery in beagle dogs. (2) To compare the ketorolac initial dose and resultant concentrations from the above study to those achieved in aqueous and vitreous by topical administration in patients undergoing cataract surgery or vitrectomy, respectively.

Methods: Lens replacement surgery with phacoemulsification was performed in 20 female beagle dogs. A fixed combination of phenylephrine and ketorolac injection 1%/0.3% was diluted 125-fold into the balanced salt solution and delivered intracamerally during the phacoemulsification procedure. Ketorolac concentration was determined by liquid chromatography/mass spectrometry.

Results: Concentrations of ketorolac when administered by the intracameral route in the dosing solution in dogs were found to be considerably higher in both aqueous and vitreous compared to what is achieved with topical dosing in patients.

Conclusions: Adequate therapeutic concentrations of ketorolac in aqueous and vitreous humor were achieved even at 10 h postdose. Critical concentrations in the aqueous that envelopes the iris/ciliary body, which are sites of prostaglandin E2 synthesis, and the vitreous are not achieved by topical dosing in clinical studies after the surgery, but are by direct intracameral dosing as determined in this study. Based on these studies and clinical data, phenylephrine and ketorolac injection 1%/0.3% delivered during surgery as an irrigation solution may preclude the need for topically administered pre- and postoperative NSAIDs.

Keywords: NSAIDs; anti-inflammatory; cataract surgery; ketorolac; topical dosing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / analysis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cataract Extraction / adverse effects*
  • Disease Models, Animal*
  • Dogs
  • Drug Delivery Systems*
  • Female
  • Humans
  • Ketorolac / administration & dosage
  • Ketorolac / analysis
  • Ketorolac / pharmacology*
  • Lens, Crystalline / drug effects*
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / analysis
  • Ophthalmic Solutions / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ophthalmic Solutions
  • Ketorolac