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      Serum Concentration of Bevacizumab after Intravitreal Injection in Experimental Branch Retinal Vein Occlusion

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          Abstract

          Aim: To compare the serum concentration of bevacizumab after intravitreal injection of bevacizumab (IVB) in an experimental model of branch retinal vein occlusion (BRVO) with control injections in albino rats. Methods: BRVO was created in one eye of each of the 24 albino rats. Another 24 rats served as controls. The BRVO was generated by argon laser photothrombosis after intravenous injection with Rose Bengal. Three days later, IVB (5 µl) was administered to both BRVO and control eyes. The serum concentration of bevacizumab was examined at baseline, 6 h, 1 day, 3 days, 7 days, 14 days, and 28 days after IVB. Results: At baseline, no serum bevacizumab was detected in either group. The serum concentration of bevacizumab reached a peak concentration at 1 day with 5,020 ± 1,602 ng/ml in the BRVO group and 4,103 ± 1,790 ng/ml in the control group (p < 0.001). The concentration decreased subsequently on days 3, 7, 14 and 28. The serum concentration of bevacizumab was significantly higher in BRVO rats up to 28 days after IVB. Conclusions: The serum concentration of bevacizumab after IVB reached its peak on day 1 in both BRVO and control eyes. This value was significantly higher in BRVO rats than in control rats up to 28 days after intravitreal injection.

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          Most cited references23

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          Mechanisms of adverse effects of anti-VEGF therapy for cancer

          Advances in understanding the role of vascular endothelial growth factor (VEGF) in normal physiology are giving insight into the basis of adverse effects attributed to the use of VEGF inhibitors in clinical oncology. These effects are typically downstream consequences of suppression of cellular signalling pathways important in the regulation and maintenance of the microvasculature. Downregulation of these pathways in normal organs can lead to vascular disturbances and even regression of blood vessels, which could be intensified by concurrent pathological conditions. These changes are generally manageable and pose less risk than the tumours being treated, but they highlight the properties shared by tumour vessels and the vasculature of normal organs.
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            Pharmacokinetics of intravitreal bevacizumab (Avastin).

            To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin). Experimental animal study. Twenty Dutch-belted rabbits. One eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. Bevacizumab concentrations in the aqueous, vitreous, and serum. Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10 microg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 microg/ml 3 days after drug administration. A maximum serum concentration of 3.3 mug/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 microg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks. The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
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              Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.

              To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). Retrospective case-control study. Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2011
                December 2010
                11 August 2010
                : 45
                : 1
                : 31-35
                Affiliations
                aDepartment of Ophthalmology, Chang Gung Memorial Hospital, Keelung, bDepartment of Ophthalmology, Chang Gung Memorial Hospital, and cChang Gung University College of Medicine, Tao-Yuan, Taiwan, ROC
                Author notes
                *Chi-Chun Lai, MD, Department of Ophthalmology, Chang Gung Memorial Hospital, 5 Fu-Hsin St., Kwei-Shan, Tao-Yuan 333, Taiwan (ROC), Tel. +886 3 328 1200, ext. 8666, Fax +886 3 328 2978, E-Mail chichun.lai@gmail.com
                Article
                315617 Ophthalmic Res 2011;45:31–35
                10.1159/000315617
                20714188
                bfe6c50f-63e7-4716-ad82-f451b03306a3
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 October 2009
                : 05 July 2010
                Page count
                Figures: 2, References: 31, Pages: 5
                Categories
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Bevacizumab,Branch retinal vein occlusion,Hypertension

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