December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
AGN 192024 (Lumigan®): a Synthetic Prostamide Analog that Lowers Primate Intraocular Pressure by Virtue of Its Inherent Pharmacological Activity
Author Affiliations & Notes
  • DF Woodward
    Allergan Inc Irvine CA
    Biological Science
  • C Madhu
    Drug Metabolism & Pharmacokinetics
    Allergan Inc Irvine CA
  • RM Burk
    Chemical Science
    Allergan Inc Irvine CA
  • SW Andrews
    Chemical Science
    Allergan Inc Irvine CA
  • J Chen
    Allergan Inc Irvine CA
    Biological Science
  • AH Krauss
    Allergan Inc Irvine CA
    Biological Science
  • B Brar
    Drug Metabolism & Pharmacokinetics
    Allergan Inc Irvine CA
  • ME Garst
    Chemical Science
    Allergan Inc Irvine CA
  • DD S Tang-Liu
    Drug Metabolism & Pharmacokinetics
    Allergan Inc Irvine CA
  • LA Wheeler
    Allergan Inc Irvine CA
    Biological Science
  • Footnotes
    Commercial Relationships    D.F. Woodward, Allergan, Inc. E; C. Madhu, Allergan, Inc. E; R.M. Burk, Allergan, Inc. E; S.W. Andrews, Allergan, Inc. E; J. Chen, Allergan, Inc. E; A.H. Krauss, Allergan, Inc. E; B. Brar, Allergan, Inc. E; M.E. Garst, Allergan, Inc. E; D.D.S. Tang-Liu, Allergan, Inc. E; L.A. Wheeler, Allergan, Inc. E.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4110. doi:
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      DF Woodward, C Madhu, RM Burk, SW Andrews, J Chen, AH Krauss, B Brar, ME Garst, DD S Tang-Liu, LA Wheeler; AGN 192024 (Lumigan®): a Synthetic Prostamide Analog that Lowers Primate Intraocular Pressure by Virtue of Its Inherent Pharmacological Activity . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4110.

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Abstract

Abstract: : Purpose: AGN 192024 (Lumigan) is a synthetic prostamide analog and a potent and highly efficacious ocular hypotensive agent. In addition to intraocular pressure studies, ocular distribution studies were conducted in living monkeys to determine concentrations of bimatoprost in various ocular tissues over a 24 hr time course. Methods: Intraocular pressure (IOP) was measured by pneumatonometry in normal and laser-induced ocular hypertensive monkeys. In bioavailability studies 0.1% [3H-] AGN 192024 was administered bilaterally to cynomolgus monkeys and one animal was euthanized at predetermined time points (0.5, 2, 4, 6, 8 and 24 hr). A single dose and a multiple dose study (AGN 192024 administered b.i.d. for 9-1/2 days), were conducted. Samples were analyzed by HPLC with radiodetection. Results: AGN 192024 was a potent ocular hypotensive agent and significant reductions in intraocular pressure were achieved even with a 0.001% dose in both ocular normotensive and ocular hypertensive monkeys. The AGN 192024 distribution pattern was essentially periorbital tissues ≷ ocular surface tissues ≷ anterior segment tissues ≷ aqueous humor. Four minor metabolites were detected. Differences between AGN 192024 concentrations in the iris and ciliary body compared to the aqueous humor were striking and typically bimatoprost concentrations were 10-100 fold greater in these anterior segment tissues, notably in the multiple dose studies. Conclusion: AGN 192024 levels in the vicinity of its active site remained sufficiently elevated to account for its long-acting ocular hypotensive effects and the intact molecule appears to account for its effects on intraocular pressure. This contention is supported by the potent inherent pharmacological activity of AGN 192024.

Keywords: 541 receptors: pharmacology/physiology • 514 pharmacology • 444 intraocular pressure 
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