title: General Pharmacokinetic Model for Topically Administered Ocular Drug Dosage Forms.
abstract: In ocular drug development, an early estimate of drug behavior before any in vivo experiments is important. The pharmacokinetics (PK) and bioavailability depend not only on active compound and excipients but also on physicochemical properties of the ocular drug formulation. We propose to utilize PK modelling to predict how drug and formulational properties affect drug bioavailability and pharmacokinetics.
  
  
  
  A physiologically relevant PK model based on the rabbit eye was built to simulate the effect of formulation and physicochemical properties on PK of pilocarpine solutions and fluorometholone suspensions. The model consists of four compartments: solid and dissolved drug in tear fluid, drug in corneal epithelium and aqueous humor. Parameter values and in vivo PK data in rabbits were taken from published literature.
  
  
  
  The model predicted the pilocarpine and fluorometholone concentrations in the corneal epithelium and aqueous humor with a reasonable accuracy for many different formulations. The model includes a graphical user interface that enables the user to modify parameters easily and thus simulate various formulations.
  
  
  
  The model is suitable for the development of ophthalmic formulations and the planning of bioequivalence studies.
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), 00014, Helsinki, Finland.
authors.forename: Feng
authors.initials: F
authors.lastname: Deng
authors.affiliation: School of Pharmacy, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Ranta
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), 00014, Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kidron
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), 00014, Helsinki, Finland. arto.urtti@helsinki.fi.|School of Pharmacy, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland. arto.urtti@helsinki.fi.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D065546:Drug Liberation; D019573:Epithelium, Corneal / Q000378:metabolism; D005079:Excipients; D005469:Fluorometholone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008954:Models, Biological; D065587:Ocular Absorption; D009883:Ophthalmic Solutions; D010862:Pilocarpine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits
chemical_list: D005079:Excipients; D009883:Ophthalmic Solutions; D010862:Pilocarpine; D005469:Fluorometholone
keywords: bioequivalence; drug development; fluorometholone; ocular absorption; pilocarpine