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Bimatoprost, the prodrug of a prostaglandin analogue
  1. C B Camras1,
  2. N A Sharif2,
  3. M B Wax3,4,
  4. J Stjernschantz5
  1. 1
    Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE, USA
  2. 2
    Molecular Pharmacology Unit, Alcon Research Ltd, Fort Worth, TX, USA
  3. 3
    Research and Development, Ophthalmology Discovery Research, Alcon Laboratories, Fort Worth, TX, USA
  4. 4
    Department of Ophthalmology and Visual Sciences, University of Texas Southwestern Medical School, Dallas, TX, USA
  5. 5
    Department of Neuroscience, Uppsala University Biomedical Center, Uppsala, Sweden
  1. C B Camras, Department of Ophthalmology and Visual Sciences, 985540 Nebraska Medical Center, Omaha, NE 68198-5540, USA; cbcamras{at}unmc.edu

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We congratulate the authors of their adequately designed study1 that demonstrates the high concentration of the free acid (the product of hydrolysis) of bimatoprost (BP), an amide, in the aqueous humour of patients receiving a single drop of BP 1, 3 or 6 h prior to cataract surgery. This important study confirms the results found in previous studies.2 3 However, despite providing important confirmatory data, Cantor et al1 appear to reach conclusions that are not supported by their own data. Whereas the two previous studies2 3 conclude that BP is a prodrug that is hydrolysed to its free acid to account for its ocular hypotensive effect by activation of known F-type prostaglandin (FP) receptors, the current publication1 surprisingly concludes that BP is not a prodrug and acts directly as an amide to reduce intraocular pressure (IOP).

The clinical studies cited above13 are not the only ones that have demonstrated the hydrolysis of BP in ocular tissues. Previous studies have demonstrated its hydrolysis in vitro in rabbit, bovine and human ocular tissues47 and after topical application in vivo in rabbit and monkey ocular tissues.8 The hydrolysis of BP to produce sufficient concentrations of its very potent free acid, a well-described FP receptor agonist, provides clear evidence of its prodrug properties. Studies in FP receptor knockout mice have clearly demonstrated the importance of FP receptors for effective IOP reduction after topical application of FP receptor agonists, including BP.912

The three clinical studies13 provide very consistent data. Each demonstrates equal or higher levels of the free acid than the intact amide of BP in aqueous humour. Each demonstrates peak levels occurring within the first few hours after topical application of BP, …

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