A Prediction Model for the Intraocular Pharmacokinetics of Intravitreally Injected Drugs Based on Molecular Physicochemical Properties.

Abstract:

PURPOSE:This study was aimed at determining the intraocular pharmacokinetics based on molecular physicochemical properties in a rabbit model. METHODS:The entire dataset was obtained from previous literature, and research articles regarding 70 molecular compounds were investigated. The intravitreal half-lives in rabbit eyeballs of 22 macromolecules and 48 micromolecules were analyzed. Multiple linear regression analysis was carried out with non-collinear independent variables (molecular weight [MW] and lipophilicity) influencing intravitreal half-lives. The best-fit equations were selected based on the correlation coefficients and goodness-of-fit statistics. RESULTS:The best-fit models obtained from the entire dataset, macromolecules, and micromolecules suggest the correlation between molecular physicochemical properties (MW and lipophilicity) and intravitreal half-life. Exclusion of outlier molecules (amphotericin B and foscarnet) leads to a better-fit correlation. MW is the definite single factor affecting intravitreal half-lives of macromolecules (Log t1/2 = 0.148 + 0.370 Log MW, R2 = 0.769), while both MW and lipophilicity influence the intraocular pharmacokinetics of micromolecules (Log t1/2 = -1.213 + 0.762 Log MW - 0.115 Log p, R2 = 0.554). CONCLUSION:The present study indicates that intravitreal half-life could be predicted based on molecular physicochemical properties (MW and lipophilicity). Also, increasing MW while reducing lipophilicity would be a reliable method for prolonging the intravitreal half-life of small chemical drugs, while MW is the single major determinant for large biologic drugs.

journal_name

Ophthalmic Res

journal_title

Ophthalmic research

authors

Kim HM,Park KH,Chung JY,Woo SJ

doi

10.1159/000499529

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

41-49

issue

1

eissn

0030-3747

issn

1423-0259

pii

000499529

journal_volume

63

pub_type

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