Pharmacokinetics of Bevacizumab after Topical, Subconjunctival, and Intravitreal Administration in Rabbits

Nomoto, Hiroyuki; Shiraga, Fumio; Kuno, Noriyuki; Kimura, Erika; Fujii, Shinobu; Shinomiya, Katsuhiko; Nugent, Alex K.; Hirooka, Kazuyuki; Baba, Tetsuya

doi:10.1167/iovs.08-3148

Cited by 249 publications

(218 citation statements)

References 52 publications

Supporting

Mentioning

190

Contrasting

Unclassified

Order By: Relevance

“…However, a longer half-life in ocular tissues after subconjunctival injection bevacizumab compared with intravitreal injection or even topical application via eye drops suggests that bevacizumab accumulates in the scleral matrix. 12 Attempting to control excessive scarring during the shortto-medium term after surgery is associated with higher success rates, and instances in which failing surgeries were rescued by using subsequent procedures have been described over the last 20 years. 21,22 After considering some pharmacokinetic issues and the necessity of the prolonged release of antiscarring drugs during the trabeculectomy postoperative period, we proposed the use of subconjunctival implants as a new bevacizumab delivery system.…”

Section: Discussionmentioning

confidence: 99%

“…One possibility is subconjunctival delivery, but it is expected to have a short duration of action and would therefore require repetitive injections. 12 Polyurethane implants (PUIs) have been investigated extensively for use in biomedical applications as scaffolds for tissue regeneration and as controlled-/sustained-release drug delivery systems because of their excellent biocompatibility, chemical versatility, and mechanical properties. [13][14][15] No previous study has evaluated the use of anti-VEGF antibodies associated with PUIs in the eye, so the aim of the present study was to demonstrate the release of active bevacizumab from PUIs in an experimental model of glaucomafiltering surgery in rabbits.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Paula

Ribeiro

Chahud

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Purpose: Vascular endothelial growth factor (VEGF) may contribute to the scarring process resulting from glaucoma filtration surgery, since this cytokine may stimulate fibroblast proliferation. The aim of this study was to describe a new bevacizumab-loaded polyurethane implant (BPUI) and to evaluate its effectiveness as a new drug delivery system of anti-VEGF antibody in a rabbit model of glaucoma filtration surgery. Methods: An aqueous dispersion of polyurethane was obtained via the conventional process. Bevacizumab (1.5 mg) was then incorporated into the dispersion and was subsequently dried to form the polymeric films. Films with dimensions of 3 · 3 · 1 mm that either did (group BPUI, n = 10) or did not contain bevacizumab (group PUI, n = 10) were implanted in the subconjunctival space, at the surgical site in 1 eye of each rabbit. The in vitro bevacizumab release was evaluated using size-exclusion high-performance liquid chromatography (HPLC), and the in vivo effects of the drug were investigated in a rabbit experimental trabeculectomy model by examining the bleb characteristics and collagen accumulation, and by performing immunohistological analyses of VEGF expression. Results: HPLC showed that only 10% of the bevacizumab in the implants had been released by postoperative day 5. In vivo studies demonstrated that the drug had no adverse effects; however, no significant differences in either the bleb area score or the collagen deposit intensity between the group PUI and the group that BPUI were observed. Moreover, the group BPUI presented a significantly lower proportion of VEGF-expressing fibroblasts than group PUI (0.17 -0.03 vs. 0.35 -0.05 cells/field, P = 0.005). Conclusions: This study demonstrated that bevacizumab release from the BPUIs only occurred for a short time probably from the surface of the films. Nevertheless, they were well tolerated in rabbit eyes and reduced the number of VEGF-expressing fibroblasts.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Paula

Ribeiro

Chahud

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

show abstract

“…systemic circulation. For example, Nomoto et al have reported that plasma concentrations of bevacizumab increase immediately after subconjunctival administration in rabbits 17 . In the present study, antibody concentrations in the plasma had increased by 3 h after injection data not shown , and concentrations in the contralateral retina increased similar to those in the injected eye Table 1 .…”

Section: Discussionmentioning

confidence: 99%

Effects of Subconjunctival Injection of Anti-Vascular Endothelial Growth Factor Antibody on Oxygen-Induced Ischemic Retinopathy in a Neonatal Rat Model

Kabayama

Saito

Nakanishi–Ueda

et al. 2012

Showa Univ J Med Sci

View full text Add to dashboard Cite

:The present study investigated the effects of subconjunctival injections of an anti-rat vascular endothelial growth factor anti-VEGF antibody on oxygen-induced retinopathy OIR in a neonatal rat model. OIR was induced by daily cycles of 80 oxygen 20.5 h , room air 0.5 h , and a progressive return to 80 oxygen 3 h for 12 days until postnatal day P 12 . On P12, rats received subconjunctival injections in their right eye of 0.1 or 1.0 g anti-VEGF antibody or 1.0 g goat IgG as a control . No injections were made into the left eye. On P18, rats were killed and their retinas were removed and at-mounted before being stained with adenosine diphosphatase. Retinal neovascularization NV was scored and the extent of avascular areas, as a percentage of total retinal area AVA , was determined using image analysis. Although there was a tendency for lower mean NV scores in eyes injected with 0.1 and 1.0 g anti-VEGF compared with control 4.3 1.1, 2.3 1.0, and 6.7 1.3, respectively ; n 10-13 , the difference failed to reach statistical signi cance. Similarly, although there was a tendency for mean AVA to be lower in the injected eyes for both the 0.1 and 1.0 g anti-VEGF groups compared with control 15 3 , 13 3 , and 25 4 , respectively ; n 10-13 , the differences were not signi cant. Similar tendencies were observed in the contralateral eyes. Although further studies using larger numbers of rats are needed to obtain statistically signi cant results, the results of the present study suggest that the subconjunctival injection of anti-VEGF antibody may prove to be a useful route of administration in conjunction with intravitreal injections, which are the generally used method at present. However, careful attention should be paid to the possibility of systemic side effects.

show abstract

“…It is easy and noninvasive. Intravitreal and subconjunctival injections achieved a high concentration in plasma and also in the fellow eye through systemic circulation after being absorbed systemically [42].…”

Section: Discussionmentioning

confidence: 99%

Post-trabeculectomy topical bevacizumab preventing bleb failure: a preliminary study

Bhasker

Saxena

Singh

2012

j ocul biol dis inform

View full text Add to dashboard Cite

This study aims to evaluate the efficacy and safety of post-trabeculectomy topical bevacizumab, in preventing bleb failure. A total of 11 females and 12 males were enrolled for the study. After a complete ophthalmic evaluation, the patients underwent trabeculectomy. Full ophthalmic examination was done the next day, which included visual acuity, intraocular pressure (IOP), and bleb morphology. Next, two drops of bevacizumab [0.25 mg (0.01 ml)] were instilled over the wound area with a tuberculin (1 ml) syringe. Pressure was applied at the medial canthus to prevent it from going into the lacrimal passage. Similar postoperative procedures were repeated at 1, 2, 3, and 4 weeks. So in all, five instillations of bevacizumab were completed. Later, the patients were followed at 1-month interval for 6 months. Target IOP was achieved in all eyes and was maintained during the study period of 6 months without any anti-glaucoma medication. Average IOP before trabeculectomy was 27.27±8.92 mmHg, which decreased postoperatively to 8.77±0.97 mmHg at 3 months and 9.27±1.16 mmHg at 6 months. This drop in IOP was statistically significant on both occasions (p=0.00). A nice low filtering bleb was formed after the surgery, and it remained the same during the study period. The other parameters like cup-to-disc ratio and visual field did not change during the 6 months of study as expected because glaucoma is a slow progressive disease. Modulating the wound at multiple sites by bevacizumab (inflammation, proliferative, and remodeling stages) can lead to success of trabeculectomy.

show abstract

Pharmacokinetics of Bevacizumab after Topical, Subconjunctival, and Intravitreal Administration in Rabbits

Cited by 249 publications

References 52 publications

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Bevacizumab-Loaded Polyurethane Subconjunctival Implants: Effects on Experimental Glaucoma Filtration Surgery

Effects of Subconjunctival Injection of Anti-Vascular Endothelial Growth Factor Antibody on Oxygen-Induced Ischemic Retinopathy in a Neonatal Rat Model

Post-trabeculectomy topical bevacizumab preventing bleb failure: a preliminary study

Contact Info

Product

Resources

About