Pharmacokinetics of Intravitreal Bevacizumab (Avastin)
TL;DR: The vitreous half-life of 1.25 mg intravitreal bevacizumab (Avastin) is 4.32 days in a rabbit eye, compared with 4.88 days and 6.86 days for the aqueous and serum values, respectively.
About: This article is published in Ophthalmology.The article was published on 2007-05-01. It has received 673 citations till now.
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TL;DR: Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease, and conventional laser Therapy led to permanent destruction of the peripheral retina.
Abstract: Background Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. Methods We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstru...
1,137 citations
TL;DR: Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 microg/ml ranibzumab were maintained in the Vitreous humor for 29 days, whereas small amounts of intravitreal bevacizumAB have been detected in the serum and fellow uninjected eye.
493 citations
TL;DR: This article aims to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment, based on the literature and unpublished data from the authors' laboratory.
407 citations
Cites result from "Pharmacokinetics of Intravitreal Be..."
...…has also been used as an argument for posterior elimination of bevacizumab, but this study is an outlier; three other rabbit and human studies indicate an anterior elimination (Bakri et al., 2007; Krohne et al., 2008; Meyer et al., 2011) (for detailed data analyses, see del Amo and Urtti (2015))....
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TL;DR: VEGF Trap maintains significant intravitreal VEGF-binding activity for 10–12 weeks after a single injection using a time-dependent and dose-dependent mathematical model.
Abstract: Aim: To compare the intravitreal binding activity of VEGF Trap with that of ranibizumab against vascular endothelial growth factor (VEGF) using a time-dependent and dose-dependent mathematical model. Methods: Intravitreal half-lives and relative equimolar VEGF-binding activities of VEGF Trap and ranibizumab were incorporated into a first-order decay model. Time-dependent VEGF Trap activities (relative to ranibizumab) for different initial doses (0.5, 1.15, 2 and 4 mg) were calculated and plotted. Results: Seventy-nine days after a single VEGF Trap (1.15 mg) injection, the intravitreal VEGF-binding activity would be comparable to ranibizumab at 30 days. After injection of 0.5, 2 and 4 mg VEGF Trap, the intravitreal VEGF-binding activities (comparable to ranibizumab at 30 days) would occur at 73, 83 and 87 days, respectively Conclusion: On the basis of this mathematical model, VEGF Trap maintains significant intravitreal VEGF-binding activity for 10–12 weeks after a single injection.
345 citations
Cites background from "Pharmacokinetics of Intravitreal Be..."
...A pharmacokinetic single-compartment rabbit model showed that intravitreal bevacizumab concentration decreases according to first-order decay.(9) Therefore, after a 1....
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TL;DR: Investigation of intraocular concentrations and pharmacokinetics of bevacizumab after a single intravitreal injection in humans found that in human nonvitrectomized eyes, the aqueous half-life of 1.5 mgintravitreally injected bevacsimab is 9.82 days.
344 citations
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TL;DR: An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.
Abstract: To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.
938 citations
TL;DR: Short-term results suggest that intravitreal bevacizumab is well tolerated and associated with a rapid regression of retinal and iris neovascularization secondary to PDR, and lower doses may achieve a therapeutic result with less risk of systemic side effects.
761 citations
TL;DR: A retrospective study of patients with CNV secondary to AMD who were treated with intravitreal injection of bevacizumab during a 3-month period found no apparent short-term safety concerns and treated eyes had a significant decrease in macular thickness and improvement in visual acuity.
Abstract: Purpose:To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).Methods:We conducted a retrospective study of patients wi
647 citations
TL;DR: In this paper, the authors evaluated the pharmacokinetic and serum bioavailability of ranibizumab after a single intravitreal (ITV) or intravenous (IV) dose in cynomolgus monkeys.
Abstract: PURPOSE Ranibizumab (rhuFab V2; Lucentis, Genentech, South San Francisco, CA) is a humanized monoclonal antibody fragment designed to bind all forms of VEGF, thereby blocking vessel permeability and angiogenesis in neovascular age-related macular degeneration. This study evaluated the pharmacokinetic (PK) and serum bioavailability of ranibizumab after a single intravitreal (ITV) or intravenous (IV) dose in cynomolgus monkeys. METHODS Monkeys received ranibizumab as either a bilateral ITV dose (500 or 2000 microg/eye; n = 6/group) or a single IV dose (1000 or 4000 microg/animal; n = 4/group). After ITV administration, ranibizumab concentrations were measured in several ocular compartments and in serum for 10 days and, after IV administration, for 48 hours. Pharmacokinetic parameters were estimated by compartmental and noncompartmental methods. RESULTS Ranibizumab cleared in parallel from all ocular compartments, with a terminal half-life of approximately 3 days. It distributed rapidly to the retina (6-24 hours), and concentrations were approximately one third that in the vitreous. After ITV injection, bioavailability (F) was 50% to 60%. Serum concentrations were very low, reflecting wider distribution and faster clearance when ranibizumab reached the serum. After IV administration, the terminal half-life was approximately 0.5 day. CONCLUSIONS This study demonstrates that ranibizumab has a PK profile that is favorable for its clinical use in treating neovascular AMD by monthly ITV injection.
538 citations
TL;DR: A set of programs is presented which has been developed for parameter estimation and simulation of models arising from pharmacokinetic applications and has been written for an interactive time-sharing environment with the experimental data and model equations stored in files for future use.
516 citations