The Hydrolysis of Bimatoprost in Corneal Tissue Generates a Potent Prostanoid FP Receptor Agonist☆

Abstract 

Using human and bovine corneal tissue, we investigated the in vitro metabolism of bimatoprost (17-phenyl-18,19,20-trinor-prostaglandin F_2α ethyl amide, Lumigan (Allergan, Inc, Irvine, CA). Enzymatic amidase activity, which converts bimatoprost to the corresponding prostaglandin carboxylic acid, was found to be present in corneal tissue from both species. Using HPLC and mass spectrometry for analyses, conversion of bimatoprost to 17-phenyl-18,19,20-trinor prostaglandin F_2α continued for at least 24 hours after excision of the cornea, with a conversion rate of approximately 25 μg/24 hours. This hydrolysis product 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. 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.

Keywords:  bimatoprost, cornea, FP receptor, glaucoma, hydrolysis, prostaglandin