Pharmacokinetics of Intravitreal Bevacizumab (Avastin)

Bakri, Sophie J.; Snyder, Melissa R.; Reid, Joel M.; Pulido, José S.; Singh, Ravinder J.

doi:10.1016/j.ophtha.2007.01.017

Cited by 636 publications

(478 citation statements)

References 21 publications

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“…The observed increase in VA is also closely similar to the increase of 10.8 ETDRS letters after ranibizumab three times and additional injections when necessary based on OCT and VA change [21]. It is interesting to see that in the 1-year follow-up study of Bashur et al, fewer injections were needed than in the 1-year follow-up study on ranibizumab of Fung et al, with almost the same criteria for reinjection, knowing that the intravenous half-life of bevacizumab is 150% that of ranibizumab in rabbit eyes [5,6,8,21]. However, the dosage in Bashur's study was 2.5 mg bevacizumab.…”

Section: Discussionmentioning

confidence: 99%

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration

Schouten

Heij

Webers

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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Aim To provide evidence for the effect of bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in exudative age-related macular degeneration Methods A systematic review of all articles of bevacizumab for exudative AMD was conducted. Articles published up to March 2008 were identified in Medline, Embase, the Cochrane Controlled Trials Register and references from included articles. Search terms were "Bevacizumab or Avastin" and "Macula* or ARMD or AMD or intra(-) vitreal or intra(-)vitreous". Three observers participated in the data retrieval and assignment of the quality scores. Results A total of 561 articles were retrieved. Three randomised controlled trials (RCT) and 23 before-and-after studies of patients (n=1,435) who had received bevacizumab were published. Inclusion criteria varied. Lack of masking was the main methodological shortcoming. These RCTs showed that bevacizumab is more effective than PDT. Bevacizumab was given intravenously or as intravitreal injection. The latter was given once, or repeatedly every 4 weeks, and with or without additional injection when a recurrence occurred, mostly based on visual acuity and/or findings from optical coherence tomography. After intravenous administration, the weighted mean change in VA was +12.8 ETDRS letters (range +11 to +14) and the weighted mean change for CRT was −129 μm (range −100 to −202). For the 23 studies with intravitreal injections, the change in VA was +8.6 letters (range +2 to +26) and the change in CRT was −90 μm (range −46 to −190). The incidence of adverse events was low. The change in VA was 2.7 letters higher for studies with a higher quality vs lower quality. Conclusion Visual acuity improves and central retinal thickness decreases in patients with exudative AMD after bevacizumab. There is no reasonable doubt that this is caused by bevacizumab. It is likely that a randomised controlled trial will show that bevacizumab is equivalent in effect to ranibizumab, which showed a change in ETDRS of +5.9 letters for occult or minimally classic CNV and +9.8 letters for classic CNV after three monthly injections in two large RCTs.

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Section: Discussionmentioning

confidence: 99%

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration

Schouten

Heij

Webers

et al. 2008

Graefes Arch Clin Exp Ophthalmol

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“…[10][11][12] However, its half-life in vitreous is as short as 4.32 days and its effective concentration is maintained for 30 days, thus multiple injection is usually required for maintaining its effect. 13 Multiple injections of bevacizumab increase the risk of injection-related complications such as vitreous hemorrhage, retinal detachment, and endophthalmitis, and it can be an economic burden to patients.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy of intravitreal bevacizumab with single simultaneous posterior subtenon triamcinolone acetonide for macular edema due to branch retinal vein occlusion

Moon

Kim

Sagong

2016

Eye

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Purpose To evaluate efficacy and safety of combination therapy of intravitreal bevacizumab (IVB) with single simultaneous posterior subtenon triamcinolone acetonide (STA) for treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods This was a prospective, randomized, interventional comparative study conducted in 45 eyes with ME secondary to BRVO who were treated primarily with IVB 1.25 mg (23 eyes, IVB group) or combination therapy of IVB 1.25 mg with a single simultaneous STA 40 mg (18 eyes, IVB/STA group). Reinjections were performed with IVB if optical coherence tomography (OCT) showed recurrent ME associated with decreased visual acuity. The main outcome measurement was the number of additional IVB injections, and changes of best-corrected visual acuity (BCVA) and central macular thickness (CMT) during a 6-month follow-up period were compared. Results BCVA showed significant improvement in two groups at 6 months. In addition, CMT showed significant decrease in two groups at 6 months. No significant differences in the change of BCVA and CMT at 6 months after injection (P = 0.973, P = 0.639) were observed between the two groups. A statistically significant difference was found regarding the number of additional IVB injections (IVB group 0.96 ± 0.83; IVB/STA group 0.44 ± 0.70, P = 0.034).Conclusion Although combination therapy of IVB with a single simultaneous STA for treatment of ME secondary to BRVO did not affect the visual outcomes compared with IVB monotherapy, it had a benefit of reducing the number of additional IVB injections.

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“…17,18 VEGF acts via VEGFR2, promoting NO synthase expression and NO activity. 16 Previous studies have reported that VEGF-exposed human endothelial cells release NO.…”

Section: Discussionmentioning

confidence: 99%

Effects of intravitreal injection of bevacizumab on nitric oxide levels

Dinç

Yıldırım

Ayaz

et al. 2014

Eye

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Purpose This study aimed to determine the possible effects of single-dose intravitreal bevacizumab on nitric oxide (NO) levels in serum and remote organs and to reveal one of the possible mechanisms in the pathophysiology of hypertension. Methods Thirty-eight adult New Zealand albino rabbits were divided into a control group (no injection was performed, killed on day 28 of the study), group 1 (killed on day 1 of the study), group 2 (killed on day 7 of the study), group 3 (killed on day 14 of the study), and group 4 (killed on day 28 of the study). The right eyes of the animals in groups 1-4 received an intravitreal single injection of 1.25 mg (0.05 ml) bevacizumab (Avastin), and their brain, heart, liver, kidney, and blood samples were collected. NO levels were evaluated in the serum and organ homogenates. Kidney tissues were assessed by electron microscopy. Results Serum, brain, kidney, and liver NO levels significantly decreased in groups 2, 3, and 4 as compared with the control group (Po0.05). In addition, heart NO levels significantly decreased in groups 3 and 4 compared with the control group (Po0.05). There were no electron microscopic changes in the kidneys of either group. Conclusions This study demonstrated that single intravitreal injection of bevacizumab decreased NO levels in serum, brain, heart, liver, and kidneys. In addition, there were no electron microscopic changes in the kidneys.

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Pharmacokinetics of Intravitreal Bevacizumab (Avastin)

Cited by 636 publications

References 21 publications

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration

A systematic review on the effect of bevacizumab in exudative age-related macular degeneration

Combination therapy of intravitreal bevacizumab with single simultaneous posterior subtenon triamcinolone acetonide for macular edema due to branch retinal vein occlusion

Effects of intravitreal injection of bevacizumab on nitric oxide levels

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