title: Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts.
abstract: To determine whether adverse effects such as elevated intraocular pressure and cataracts, which are lower with dexamethasone when compared with fluocinolone acetonide or triamcinolone acetonide, may be explained in part by the differences in drug lipophilicity and partitioning of these drugs into the trabecular meshwork and lens.
  
  
  
  The n-octanol/phosphate-buffered saline (pH 7.4) partition coefficient (log distribution coefficient [D]) and bovine/human ocular tissue partition coefficients were determined for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide at 37°C.
  
  
  
  The log D of the corticosteroids ranged from 0.712 to 2.970. The ranges of tissue:PBS partition coefficients following drug incubation at 0.4, 2.0, and 10.0 μg/mL were 0.35 to 1.56, 0.30 to 2.12, and 0.30 to 1.95, respectively, for the bovine lens, 0.87 to 4.18, 0.71 to 4.40, and 0.69 to 5.86, respectively, for the human lens, and 2.98 to 9.48, 2.41 to 9.16, and 1.71 to 9.96, respectively, for the bovine trabecular meshwork. In general, tissue partitioning showed a positive correlation with log D. Dexamethasone, with lipophilicity less than triamcinolone acetonide and fluocinolone acetonide, exhibited the least amount of partitioning in the trabecular meshwork and lens among these 3 corticosteroids commonly used for treating diseases at the back of the eye.
  
  
  
  Binding of corticosteroids to the trabecular meshwork and lens increases as drug lipophilicity increases.
  
  
  
  Less lipophilic corticosteroids with limited partitioning to the trabecular meshwork and lens may result in reduced incidence of elevated intraocular pressure and cataracts.
authors.affiliation: Nanomedicine and Drug Delivery Laboratory, Department of Pharmaceutical Sciences, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Thakur
authors.forename: Rajendra
authors.initials: R
authors.lastname: Kadam
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
mesh_terms: D000818:Animals; D019819:Budesonide / Q000737:chemistry / Q000378:metabolism; D002386:Cataract / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000737:chemistry / Q000378:metabolism; D005446:Fluocinolone Acetonide / Q000737:chemistry / Q000378:metabolism; D005938:Glucocorticoids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D007908:Lens, Crystalline / Q000737:chemistry* / Q000378:metabolism; D008875:Middle Aged; D011239:Prednisolone / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014129:Trabecular Meshwork / Q000737:chemistry* / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000737:chemistry / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D005446:Fluocinolone Acetonide; D019819:Budesonide; D003907:Dexamethasone; D011239:Prednisolone; D014222:Triamcinolone Acetonide