title: Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits.
abstract: OBJECTIVE
  To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection.
  
  
  METHODS
  Fifty-four New Zealand white rabbits received ketorolac (250 μg/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina-choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated.
  
  
  RESULTS
  The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 μg/mL and 3.15 ± 0.49 μg/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 μg/mL (at 0.5 hours) and 208.0 ± 21.67 μg/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 μg/mL and 56.71 ± 22.64 μg/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0-t) in group B (866.1 ± 52.67 μg/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 μg/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 μg/g was detected in the RC in group C. Plasma concentrations were below 0.4 μg/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection.
  
  
  CONCLUSIONS
  Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.
authors.affiliation: Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China.
authors.forename: Meizi
authors.initials: M
authors.lastname: Wang
authors.forename: Wu
authors.initials: W
authors.lastname: Liu
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Lu
authors.forename: Huiyang
authors.initials: H
authors.lastname: Zeng
authors.forename: Sumeng
authors.initials: S
authors.lastname: Liu
authors.forename: Yankun
authors.initials: Y
authors.lastname: Yue
authors.forename: Haiting
authors.initials: H
authors.lastname: Cheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002829:Choroid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004333:Drug Administration Routes; D006207:Half-Life; D020911:Ketorolac Tromethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020911:Ketorolac Tromethamine