title: Intraocular metabolites of isopropyl unoprostone.
abstract: OBJECTIVE
  It is still unknown which metabolite of isopropyl unoprostone is responsible for reducing intraocular pressure. This study was carried out to measure intraocular metabolites of isopropyl unoprostone in the aqueous humor of primate and human eyes.
  
  
  METHODS
  Nine monkeys were randomly divided into three groups, all of which received isopropyl unoprostone. In group I, the drug was scheduled to be instilled at 0 hr, in group II at 1 hr, and in group III at 2 hr, prior to aqueous humor aspiration in order to determine metabolite concentration. Furthermore, 27 patients scheduled for cataract surgery and intraocular lens implantation were divided into five groups that received isopropyl unoprostone. In group A, the drug was scheduled to be instilled at 0 hr, in group B at 1 hr, in group C at 2 hr, in group D at 3 hr, and in group E at 4 hr, prior to surgery. At the beginning of the operation, the aqueous humor was aspirated. Metabolites of isopropyl unoprostone in the aqueous humor were determined by high-performance liquid chromatography.
  
  
  RESULTS
  M1 (3-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]propionic acid) (unoprostone free acid) and M2 ((Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid), an intraocular oxidized metabolite of isopropyl unoprostone, were measured. M1:M2 in monkeys was respectively 0:0 ng/ml in group I, 150.2 +/- 45.1:9.5 +/- 1.7 (p < 0.05) in group II, and 74.6 +/- 31.4:19.2 +/- 5.3 (p < 0.01) in group III. M1:M2 in humans was respectively 0:0 ng/ml in group A, 50.6 +/- 22.3:3.2 +/- 1.3 (p < 0.05) in group B, 125.0 +/- 23.1:12.2 +/- 3.4 (p < 0.001) in group C, 144.9 +/- 33.8:24.5 +/- 6.2 (p < 0.01) in group D, and 56.7 +/- 21.5:18.7 +/- 5.3 (p < 0.05) in group E.
  
  
  CONCLUSIONS
  A free acid of isopropyl unoprostone is the major intraocular metabolite of isopropyl unoprostone that is expected to act on target tissues in the eyes of both monkeys and humans.
authors.affiliation: Division of Ophthalmology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. jnumaga@mub.biglobe.ne.jp
authors.forename: Jiro
authors.initials: J
authors.lastname: Numaga
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koseki
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Kaburaki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kawashima
authors.forename: Goji
authors.initials: G
authors.lastname: Tomita
authors.forename: Makoto
authors.initials: M
authors.lastname: Araie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007322:Instillation, Drug; D008252:Macaca fascicularis; D008297:Male; D010084:Oxidation-Reduction
chemical_list: C507874:3-(3,5-dihydroxy-2-(oxodecyl)cyclopentyl)propionic acid; C507875:7-(3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl)hept-5-enoic acid; C072630:isopropyl unoprostone; D015237:Dinoprost