title: Pharmacokinetic prediction of the ocular absorption of an instilled drug with ophthalmic viscous vehicle.
abstract: We previously developed an in vivo pharmacokinetic model that accounts for the corneal diffusion in albino rabbits and predicts the concentration of beta-blockers in the anterior segments. The purpose of this study is to pharmacokinetically predict the ocular absorption and characterize the systemic absorption of instilled drug with ophthalmic viscous vehicle to assist in its design and evaluation. Tilisolol and carboxymethylcellulose sodium salt (CMC) were used as the model ophthalmic drug and viscous polymer, respectively. After instillation of tilisolol with CMC vehicle in rabbits, the disposition of the drug in tear fluid, aqueous humor, and plasma were determined by HPLC. The ocular and systemic absorption were analyzed by a mathematical model including a diffusion process and a two-compartment model with first-order absorption, respectively. CMC vehicle increased the area under the concentration-time curve (AUC) of tilisolol in the tear fluid and aqueous humor and slightly reduced the AUC in plasma. The concentrations of tilisolol in the aqueous humor after instillation with CMC vehicle were accurately predicted from the tear concentrations by using the in vivo ocular pharmacokinetic model. CMC vehicle improved the ocular delivery of tilisolol.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. sasaki@net.nagasaki-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Yamamura
authors.forename: T
authors.initials: T
authors.lastname: Mukai
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Ichikawa
mesh_terms: D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D019540:Area Under Curve; D002266:Carboxymethylcellulose Sodium; D005123:Eye / Q000378:metabolism*; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D009883:Ophthalmic Solutions; D010592:Pharmaceutic Aids; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D013666:Tears / Q000737:chemistry; D014783:Viscosity
chemical_list: D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D009883:Ophthalmic Solutions; D010592:Pharmaceutic Aids; D014677:Pharmaceutical Vehicles; D002266:Carboxymethylcellulose Sodium; C036593:tilisolol