title: Aqueous levels of fluocinolone acetonide after administration of fluocinolone acetonide inserts or fluocinolone acetonide implants.
abstract: OBJECTIVE
  To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY).
  
  
  METHODS
  Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials.
  
  
  METHODS
  Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318).
  
  
  METHODS
  Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts.
  
  
  METHODS
  The primary end point was aqueous levels of FAc.
  
  
  RESULTS
  At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes.
  
  
  CONCLUSIONS
  Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
authors.affiliation: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gulnar
authors.initials: G
authors.lastname: Hafiz
authors.affiliation: Bennett and Bloom Eye Centers, Louisville, Kentucky.
authors.forename: Steven
authors.initials: S
authors.lastname: Bloom
authors.affiliation: Retinal Consultants of Houston, Houston, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.affiliation: Associates in Ophthalmology, Pittsburgh, Pennsylvania.
authors.forename: Miguel
authors.initials: M
authors.lastname: Busquets
authors.affiliation: Midwest Eye Institute, Indianapolis, Indiana.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciulla
authors.affiliation: Retina Associates of New Jersey, Teaneck, New Jersey.
authors.forename: Leonard
authors.initials: L
authors.lastname: Feiner
authors.affiliation: Department of Ophthalmology, University of Missouri-Kansas City School of Medicine, Truman Medical Centers, Kansas City, Missouri.
authors.forename: Nelson
authors.initials: N
authors.lastname: Sabates
authors.affiliation: Alimera Sciences, Inc., Alpharetta, Georgia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Billman
authors.affiliation: Alimera Sciences, Inc., Alpharetta, Georgia.
authors.forename: Barry
authors.initials: B
authors.lastname: Kapik
authors.affiliation: Alimera Sciences, Inc., Alpharetta, Georgia.
authors.forename: Ken
authors.initials: K
authors.lastname: Green
authors.affiliation: Alimera Sciences, Inc., Alpharetta, Georgia.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Kane
mesh_terms: D001082:Aqueous Humor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003930:Diabetic Retinopathy / Q000378:metabolism; D004343:Drug Implants; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008269:Macular Edema / Q000378:metabolism; D013058:Mass Spectrometry; D011446:Prospective Studies; D014605:Uveitis / Q000378:metabolism
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide