title: Pharmacokinetic aspects of retinal drug delivery.
abstract: Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Del Amo
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Rimpelä
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Heikkinen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Otto K
authors.initials: OK
authors.lastname: Kari
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Eva
authors.initials: E
authors.lastname: Ramsay
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Tatu
authors.initials: T
authors.lastname: Lajunen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Pelkonen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Madhushree
authors.initials: M
authors.lastname: Bhattacharya
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Richardson
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Subrizi
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Turunen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Reinisalo
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Itkonen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Toropainen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Marco
authors.initials: M
authors.lastname: Casteleijn
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kidron
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Maxim
authors.initials: M
authors.lastname: Antopolsky
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kati-Sisko
authors.initials: KS
authors.lastname: Vellonen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marika
authors.initials: M
authors.lastname: Ruponen
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland. Electronic address: arto.urtti@helsinki.fi.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D058449:Intravitreal Injections; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Choroid; Clearance; Distribution; Intravitreal; Pharmacokinetic modeling; Retina; Sub-conjunctival; Suprachoroidal; Topical; Transport; Vitreous