Hydrolysis of bimatoprost (Lumigan) to its free acid by ocular tissue in vitro.

Davies SS, Ju WK, Neufeld AH, Abran D, Chemtob S, Roberts LJ
J Ocul Pharmacol Ther. 2003 19 (1): 45-54

PMID: 12648303 · DOI:10.1089/108076803762718105

We determined whether bimatoprost, which has been reported to act via putative prostamide receptors, could be hydrolyzed to its free acid (17-phenyl-PGF(2 alpha)), a potent FP receptor agonist, by human ocular tissue in vitro. We developed a gas chromatography/mass spectrometric method to measure 17-phenyl-PGF(2 alpha) levels at sub-picomolar levels. We then analyzed the amount of 17-phenyl-PGF(2 alpha) present after incubation of 50 microl Lumigan (0.03% bimatoprost) with eye tissue using this assay. We found that cornea, sclera, iris, and ciliary body, all rapidly hydrolyzed bimatoprost to 17-phenyl-PGF(2 alpha) with linear kinetics at a rate of 6.3, 2.0, 2.8, and 1.5 pmol mg tissue(-1) hr(-1), respectively. For cornea, sclera, and ciliary body, this linear rate of hydrolysis continued over a period of at least three hours, while iris-induced hydrolysis did not continue beyond one hour. Our findings suggest that bimatoprost can act as prodrug for FP receptor activation and questions the concept of a "prostamide receptor" agonist.

MeSH Terms (19)

Amides Animals Bimatoprost Ciliary Body Cloprostenol Cornea Dinoprost Eye Humans Hydrolysis In Vitro Techniques Iris Kinetics Lipid Metabolism Lipids Prodrugs Sclera Swine Time Factors

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