title: Comparison of human ocular distribution of bimatoprost and latanoprost.
abstract: OBJECTIVE
  This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration-activity relationships.
  
  
  METHODS
  Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body.
  
  
  CONCLUSIONS
  Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.
authors.affiliation: Anne V. Goldberg Glaucoma Service, Willis Eye Institute, Philadelphia, PA, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Ichhpujani
authors.forename: L Jay
authors.initials: LJ
authors.lastname: Katz
authors.forename: Gabor
authors.initials: G
authors.lastname: Hollo
authors.forename: Carol L
authors.initials: CL
authors.lastname: Shields
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Shields
authors.forename: Brian
authors.initials: B
authors.lastname: Marr
authors.forename: Ralph
authors.initials: R
authors.lastname: Eagle
authors.forename: Heryberto
authors.initials: H
authors.lastname: Alvim
authors.forename: Sheryl S
authors.initials: SS
authors.lastname: Wizov
authors.forename: Andrew
authors.initials: A
authors.lastname: Acheampong
authors.forename: June
authors.initials: J
authors.lastname: Chen
authors.forename: Larry A
authors.initials: LA
authors.lastname: Wheeler
mesh_terms: D000577:Amides / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D000069580:Bimatoprost; D002851:Chromatography, High Pressure Liquid; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005123:Eye / Q000378:metabolism*; D015353:Eye Enucleation; D006801:Humans; D000077338:Latanoprost; D057230:Limit of Detection; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D003008:Cloprostenol; D000077338:Latanoprost; D000069580:Bimatoprost