Binding of Small Molecule Drugs to Porcine Vitreous Humor

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Rimpelä , A-K , Reunanen , S , Hagström , M , Kidron , H & Urtti , A 2018 , ' Binding of Small Molecule Drugs to Porcine Vitreous Humor ' , Molecular Pharmaceutics , vol. 15 , no. 6 , pp. 2174-2179 .

Title: Binding of Small Molecule Drugs to Porcine Vitreous Humor
Author: Rimpelä, Anna-Kaisa; Reunanen, Saku; Hagström, Marja; Kidron, Heidi; Urtti, Arto
Contributor organization: Faculty of Pharmacy
Division of Pharmaceutical Biosciences
Drug Research Program
Drug Delivery
Drug Delivery Unit
Date: 2018-06
Language: eng
Number of pages: 6
Belongs to series: Molecular Pharmaceutics
ISSN: 1543-8384
Abstract: Pharmacokinetics in the posterior eye segment has therapeutic implications due to the importance of retinal diseases in ophthalmology. In principle, drug binding to the components of the vitreous, such as proteins, collagen, or glycosaminoglycans, could prolong ocular drug retention and modify levels of pharmacologically active free drug in the posterior eye segment. Since drug binding in the vitreous has been investigated only sparsely, we studied vitreal drug binding of 35 clinical small molecule drugs. Isolated homogenized porcine vitreous and the drugs were placed in a two compartment dialysis system that was used to separate the bound and unbound drug. Free drug concentrations and binding percentages were quantitated using LC-MS/MS. Drug binding levels varied between 21 and 74% in the fresh vitreous and 0 and 64% in the frozen vitreous. The vitreal binding percentages did not correlate with those in plasma. Our data-based pharmacokinetic simulations suggest that vitreal binding of small molecule drugs has only a modest influence on the AUC of free drug or drug half-life in the vitreous. Therefore, it is likely that vitreal binding is not a major reason for interindividual variability in ocular drug responses or drug-drug interactions.
Subject: 317 Pharmacy
retinal drug delivery
vitreal binding
ocular pharmacokinetics
drug binding
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion

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