title: Ocular pharmacokinetics comparison between 0.2% olopatadine and 0.77% olopatadine hydrochloride ophthalmic solutions administered to male New Zealand white rabbits.
abstract: OBJECTIVE
  The primary objective of this study was to compare uptake and distribution of the commercially available formulation of 0.2% olopatadine and the newly developed 0.77% olopatadine hydrochloride ophthalmic solution formulation with improved solubility following a single (30 μL), bilateral topical ocular dose in male New Zealand white rabbits.
  
  
  METHODS
  Each animal received a single 30-μL topical ocular dose (0.2% olopatadine or 0.77% olopatadine hydrochloride ophthalmic solution) to the right (OD) eye followed by the left (OS) eye for a total dose of 60 μL. Olopatadine concentrations were measured in ocular tissues (cornea, bulbar, conjunctiva, choroid, iris-ciliary body, whole lens, retina), aqueous humor, and plasma at prespecified time points over 24 h using a qualified liquid chromatography coupled with mass spectrometry (LC-MS/MS) analytical method.
  
  
  RESULTS
  Olopatadine was absorbed into the eye and reached maximal levels (Cmax) within 30 min (0.5 h) to 2 h (Tmax) in ocular tissues and plasma for both treatment groups, except for the lens in which the Tmax was 4 h in the 0.2% olopatadine group and 8 h in the 0.77% olopatadine hydrochloride group, respectively. Tissues associated with the site of dosing, that is, the conjunctiva and cornea, had the highest concentrations of olopatadine in both the 0.2% olopatadine (609 and 720 ng/g) and 0.77% olopatadine hydrochloride (3,000 and 2,230 ng/g) dose groups. The greatest differences between 0.2% olopatadine and 0.77% olopatadine hydrochloride were associated with the overall duration and level of ocular exposures.
  
  
  CONCLUSIONS
  The newly developed 0.77% olopatadine hydrochloride ophthalmic solution formulation resulted in a higher and more prolonged olopatadine concentration in the target tissue, that is, conjunctiva compared to the commercial formulation of 0.2% olopatadine ophthalmic solution.
authors.affiliation: Ocular Pharmacokinetics and Disposition Department, Alcon Research, Limited , A Novartis Company, Fort Worth, Texas.
authors.forename: Ganesh R
authors.initials: GR
authors.lastname: Iyer
authors.forename: Marita M
authors.initials: MM
authors.lastname: Cason
authors.forename: Scott W
authors.initials: SW
authors.lastname: Womble
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.forename: James E
authors.initials: JE
authors.lastname: Chastain
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D000069605:Olopatadine Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D018926:Anti-Allergic Agents; D009883:Ophthalmic Solutions; D000069605:Olopatadine Hydrochloride