title: Ocular pharmacokinetics of naringenin eye drops following topical administration to rabbits.
abstract: OBJECTIVE
  To investigate the ocular pharmacokinetics of 1% naringenin eye drops following topical administration to rabbits.
  
  
  METHODS
  One drop (50 μL) of 1% naringenin eye drops was instilled into both eyes of each rabbit. The animals were sacrificed at predetermined intervals after dosing, and ocular tissues and plasma were then collected. Concentrations of naringenin were analyzed using specific electrospray ionization liquid chromatography-tandem mass spectrometry method, which is proved to be sensitive, specific, precise, and suitable for determination of naringenin in ocular tissues and plasma of rabbits.
  
  
  RESULTS
  Ocular exposure to naringenin, based on AUC(0-t), was highest in cornea, followed by aqueous humor, retina, and vitreous body. The Cmax of naringenin in cornea, aqueous humor, vitreous body, and retina were 67945.30 ± 4109.34 ng/g, 1325.69 ± 239.34, 160.52 ± 38.78 ng/mL, and 1927.08 ± 660.77 ng/g at 0.083, 0.75, 0.083, and 0.083 h after topical administration, respectively. The half-lives for these tissues were 9.37, 0.65, 1.17, and 4.62 h, respectively. There was no significant difference between free naringenin and total naringenin in plasma based on Cmax and Tmax. Cmax of total naringenin in plasma at 0.083 h was 35.12 ± 0.54 ng/mL.
  
  
  CONCLUSIONS
  Measurable concentrations of naringenin were achieved in ocular tissues after topical application in rabbits. Topical instillation of naringenin may be an effective approach in the treatment of posterior section diseases.
authors.affiliation: 1 School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou, China .
authors.forename: Junli
authors.initials: J
authors.lastname: Lin
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.forename: Yandong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Wenpei
authors.initials: W
authors.lastname: Chen
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Gui
authors.forename: Baoqin
authors.initials: B
authors.lastname: Lin
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D005123:Eye / Q000378:metabolism*; D005260:Female; D044950:Flavanones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D011897:Random Allocation; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D009883:Ophthalmic Solutions; C005273:naringenin