December 2002
Volume 43, Issue 13
ARVO Annual Meeting Abstract  |   December 2002
The Hydrolysis of Bimatoprost in Corneal Tissue Generates a Potent Prostanoid FP Receptor Agonist
Author Affiliations & Notes
  • KM Maxey
    Cayman Chemical Company Ann Arbor MI
  • J Johnson
    Cayman Chemical Ann Arbor MI
  • J LaBrecque
    Cayman Chemical Ann Arbor MI
  • Footnotes
    Commercial Relationships    K.M. Maxey, Cayman Chemical Company E; Pharmacia C; J. Johnson, Cayman Chemical E; J. LaBrecque, Cayman Chemical E.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4071. doi:
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      KM Maxey, J Johnson, J LaBrecque; The Hydrolysis of Bimatoprost in Corneal Tissue Generates a Potent Prostanoid FP Receptor Agonist . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4071.

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

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Abstract: : Purpose: The purpose of this study was to investigate the metabolism of the prostaglandin analog bimatoprost, (17-phenyl-18,19,20-trinor-prostaglandin F-N-ethyl amide; Lumigan) in the excised human and bovine cornea. Our interest was to determine whether the free acid metabolite, resulting from hydrolysis of the C-1 ethyl amide, was generated in the cornea. Methods: We excised fresh human and bovine corneal tissue, and investigated the in vitro metabolism of bimatoprost (17-phenyl-18,19,20-trinor-prostaglandin F-N-ethyl amide; Lumigan) and other prostaglandin analogs, including latanoprost (Xalatan), prostaglandin F-1-isopropyl ester, and their free acids. The incubations were carried out in physiologic buffer at 37 degrees C. HPLC, TLC and mass spectrometry were used for analysis of the metabolite mixture. Results: Enzymatic amidase activity, which converts bimatoprost to the corresponding prostaglandin carboxylic acid, was found to be present in corneal tissue from both species. Conversion of bimatoprost to 17-phenyl-18,19,20-trinor prostaglandin F continued for at least 24 hours after excision of the cornea, with a conversion rate of approximately 2.5 µg/g/24 hours. Conclusions: The hydrolysis product of bimatoprost is identical to the free acid of latanoprost with the exception of a double, rather than a single, bond at the carbon 13-14 position. We detected sufficient amidase activity in a single human cornea to convert a significant fraction of an administered daily dose to the free acid. Assuming that this conversion also occurs in vivo at a similar rate, this hydrolysis product may account for the reduction of intraocular pressure occurring in patients treated with bimatoprost. Therefore, like latanoprost, bimatoprost appears to be a prodrug, which likely requires conversion to its free acid for its therapeutic effect.

Keywords: 374 cornea: stroma and keratocytes • 444 intraocular pressure • 503 outflow: trabecular meshwork 

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