Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.

Détails

ID Serval
serval:BIB_1178BF69C1D1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.
Périodique
Investigative Ophthalmology and Visual Science
Auteur(s)
Furrer E., Berdugo M., Stella C., Behar-Cohen F., Gurny R., Feige U., Lichtlen P., Urech D.M.
ISSN
1552-5783 (Electronic)
ISSN-L
0146-0404
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
50
Numéro
2
Pages
771-778
Langue
anglais
Notes
Publication types: Comparative Study ; Journal ArticlePublication Status: ppublish
Résumé
PURPOSE: The purpose of this study was to characterize local distribution and systemic absorption of the tumor necrosis factor (TNF)-alpha inhibitory single-chain antibody fragment (scFv) ESBA105 following topical administration to the eye in vivo.
METHODS: Rabbits received ESBA105 as topical eye drops in two dosing regimens. First, pharmacokinetics after the topical route of administration was compared to the intravenous (i.v.) route by means of applying the identical cumulative daily dose of ESBA105. In a second study rabbits received five eye drops daily for six consecutive days in a lower frequency topical dosing regimen. Kinetics and biodistribution of ESBA105 in ocular tissues and fluids as well as in sera were determined in all animals.
RESULTS: After topical administration to the eye, ESBA105 quickly reaches therapeutic concentrations in all ocular compartments. Systemic exposure after topical administration is 25,000-fold lower than exposure after i.v. injection of the identical cumulative daily dose. ESBA105 levels in vitreous humor and neuroretina are significantly higher on topical administration than after i.v. injection. Absolute and relative intraocular biodistribution of ESBA105 is different with topical and systemic delivery routes. Compared to its terminal half-life in circulation (7 hours), the vitreal half-life of ESBA105 is significantly enhanced (16-24 hours).
CONCLUSIONS: On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders.
Mots-clé
Administration, Topical, Animals, Antibodies, Monoclonal/administration & dosage, Antibodies, Monoclonal/pharmacokinetics, Aqueous Humor/metabolism, Biological Availability, Choroid/metabolism, Enzyme-Linked Immunosorbent Assay, Female, Half-Life, Immunoglobulin Fragments/immunology, Immunoglobulin Variable Region/immunology, Injections, Intravenous, Ophthalmic Solutions/administration & dosage, Ophthalmic Solutions/pharmacokinetics, Rabbits, Retina/metabolism, Retinal Pigment Epithelium/metabolism, Tissue Distribution, Tumor Necrosis Factor-alpha/immunology, Vitreous Body/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/08/2013 15:42
Dernière modification de la notice
20/08/2019 13:39
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