Universität zu Köln

Saunders, Derek J., Muether, Philipp S. and Fauser, Sascha (2015). A model of the ocular pharmacokinetics involved in the therapy of neovascular age-related macular degeneration with ranibizumab. Br. J. Ophthalmol., 99 (11). S. 1554 - 1560. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2079

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Abstract

Background To develop a model of the pharmacokinetics of vascular endothelial growth factor (VEGF-A) determined in samples of aqueous humour from patients with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis). Methods Post hoc analysis of data from 31 eyes of 31 patients with AMD treated with ranibizumab gathered in a non-randomised, prospective clinical study. VEGF-A concentrations were measured in 440 aqueous humour samples by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Results The kinetics of recovery of VEGF-A from suppression by ranibizumab were well described by a simple model: VEGF-A is produced at a constant individual rate; VEGF-A and ranibizumab disperse rapidly within the vitreous chamber and bind with a known affinity; both are eliminated at identical rates from the vitreous chamber in a constant but individual flow into the anterior chamber, and are finally cleared by draining into the peripheral circulation. Average rates of VEGF-A production were predicted to be 5.8 fmol/day (range: 2.7-10.1 fmol), and elimination half-times predicted to be 3.5 days (range: 2.3-5.5 days). The duration of complete VEGF-A suppression in the aqueous humour averaged 41 days (range: 28-67 days). Conclusions The ocular pharmacokinetics of VEGF-A and ranibizumab have been linked for the first time in a simple and plausible model which suggests that it might be possible to anticipate individual VEGF-A suppression times.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saunders, Derek J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Muether, Philipp S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-388382
DOI:	10.1136/bjophthalmol-2015-306771
Journal or Publication Title:	Br. J. Ophthalmol.
Volume:	99
Number:	11
Page Range:	S. 1554 - 1560
Date:	2015
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2079
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; SINGLE INTRAVITREAL INJECTION; AQUEOUS-HUMOR LEVELS; 2.0 MG RANIBIZUMAB; INTRAOCULAR PHARMACOKINETICS; VITREOUS LEVELS; BEVACIZUMAB; CYTOKINES; EFFICACY; BINDING Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38838