The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP receptor agonist.
Using human and bovine corneal tissue, we investigated the in vitro metabolism of bimatoprost (17-phenyl-18,19,20-trinor-prostaglandin F(2alpha) 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(2alpha) continued for at least 24 hours after excision of the cornea, with a conversion rate of approximately 25 microg/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.
Maxey
Kirk M
KM
Cayman Chemical Company, 1180 E Ellsworth Road, Ann Arbor, MI 48108, USA. kirk@caymanchem.com
Johnson
Jennifer L
JL
LaBrecque
Jennifer
J
D000577:Amides; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D000069580:Bimatoprost; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003008:Cloprostenol / Q000031:analogs & derivatives; D003315:Cornea / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006868:Hydrolysis; D050356:Lipid Metabolism; D008055:Lipids; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
D000577:Amides; D000959:Antihypertensive Agents; D008055:Lipids; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D003008:Cloprostenol; D000069580:Bimatoprost