Quantitative pharmacokinetic analyses of anterior and posterior elimination routes of intravitreal anti-VEGF macromolecules using published human and rabbit data

Lamminsalo, Marko; Urtti, Arto; Ranta, Veli‐Pekka

doi:10.1016/j.exer.2022.109162

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…These results show that including convection into our model is another way of accounting for “posterior elimination” since the drug is carried out towards the outer surface of the vitreous humor. Results show that in rabbit vitreous humor, the effect of the anterior elimination route is dominant over the posterior elimination route; this is consistent with the results from Lamminsalo et al [24].…”

Section: Resultssupporting

confidence: 92%

“…show that in rabbit vitreous humor, the effect of the anterior elimination route is dominant over the posterior elimination route; this is consistent with the results from Lamminsalo et al [24].…”

Section: Rabbit Eyesupporting

confidence: 92%

“…The drug transport through the vitreous is solved using the transport of diluted species physics in COMSOL. Our computational PK model does not include the effect of metabolism and degradation of bevacizumab as it is negligible in the eye [24].…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, a recent study observed the elimination routes of anti-VEGF therapeutics in both human and rabbit vitreous [24]. The results suggested that the anterior elimination route is domi-nant compared to the posterior route for bevacizumab and other anti-VEGF drugs in both human and rabbit eyes.…”

Section: Methodsmentioning

confidence: 99%

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Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes

Chowdhury

Swindle-Reilly

Versypt

2023

Preprint

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Macula clears our central vision and sharpens our visibility. The macula is positioned in the middle of the retinal tissue. Age-related macular degeneration (AMD) is a condition brought on by macular deterioration. In the United States, millions of elderly people suffer from AMD. There is no permanent cure if the disease is diagnosed at a later stage. AMD is an irreversible disease where the patient goes blind eternally. For retinal treatment, due to the material characteristics of the vitreous humor layer, it serves as the main barrier to drug transport to the retinal layer. Many treatments, including drug-based treatment, laser photocoagulation, and laser therapy, have been used for AMD disease. Anti-VEGF drugs have been proven most stable medication in AMD treatment that inhibits the action of vascular endothelial growth factor. One of the most suggested anti-VEGF drugs used in AMD treatment is bevacizumab using intravitreal injection. In our study, we have developed a spatially distributed pharmacokinetic model of the drug bevacizumab to measure time-drug concentration profiles throughout the vitreous and near the macula in rabbit and human eyes.

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Section: Resultssupporting

confidence: 92%

Section: Rabbit Eyesupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes

Chowdhury

Swindle-Reilly

Versypt

2023

Preprint

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“…The clinical heterogeneity among the studies was considerable in several aspects, including symptom duration before treatment, anti-VEGF agents used for IVT, inclusion criteria for eligibility, and retreatment criteria. This heterogeneity of anti-VEGF agents is especially crucial in the aspect of the injection frequency, as aflibercept and bevacizumab have longer intravitreal half-lives than ranibizumab 29 , 30 . However, real-world studies comparing between anti-VEGF agents in PRN method revealed no significant differences in the number of IVT 8 , 31 , 32 , suggesting that the injection frequency in clinical practice does not always correlate with pharmacokinetics of anti-VEGF agents.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of as-needed intravitreal injection compared to 3-monthly loading of anti-vascular endothelial growth factor agents for branch retinal vein occlusion

Younghae

Woo

Park

et al. 2023

Sci Rep

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We investigated the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents in branch retinal vein occlusion (BRVO). Databases, including PubMed, EMBASE, and the Cochrane Library, were searched on November 11, 2022. Studies comparing the pro-re-nata (PRN) regimen after the first treatment (PRN group) to three consecutive monthly injection regimens followed by the PRN regimen (3 + PRN group) were investigated. The primary outcomes were the change in best-corrected visual acuity (BCVA) and the change in central retinal thickness (CRT), with the secondary outcome being the injection frequency. Among 195 reports on anti-VEGF treatment, six comparative studies were included in this meta-analysis. The two groups had no statistically significant differences in terms of BCVA or CRT. However, the total number of injections during follow-up was significantly lower in the PRN group than in the 3 + PRN group (95% CI − 2.09 to − 0.83). The as-needed injection regimen is as effective as 3-monthly loading in terms of anatomical and functional improvement for BRVO, along with a lower treatment burden for patients and physicians.

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Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

Zhou,

Xu,

Shen

et al. 2024

Adv Healthcare Materials

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As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti‐vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which has been endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state‐of‐the‐art studies. Firstly, we thoroughly introduce the current therapeutic modalities for FNDs, focusing on the key challenges of ocular fundus drug delivery. Secondly, we comprehensively reviewed nanocarriers for ocular posterior drug delivery based on the nanostructures: polymer‐based nanocarriers, lipid‐based nanocarriers, and inorganic nanoparticles. Thirdly, we elaborate on the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.This article is protected by copyright. All rights reserved

show abstract

Quantitative pharmacokinetic analyses of anterior and posterior elimination routes of intravitreal anti-VEGF macromolecules using published human and rabbit data

Cited by 10 publications

References 31 publications

Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes

Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes

Efficacy of as-needed intravitreal injection compared to 3-monthly loading of anti-vascular endothelial growth factor agents for branch retinal vein occlusion

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

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