Comparative antiproliferative and cytotoxic profile of bevacizumab (Avastin), pegaptanib (Macugen) and ranibizumab (Lucentis) on different ocular cells

Abstract

Bevacizumab, pegaptanib and ranibizumab significantly suppress choroidal endothelial cell proliferation. However, when used at the currently established doses none of the drugs was superior over the others in respect to endothelial cell growth inhibition. The biocompatibility of all three drugs--including the off-label bevacizumab--seems to be excellent when used at the currently recommended intravitreal dose.

Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy

“…Other authors have not found the intravitreous injection of bevacizumab (which blocks all circulating VEGF isoforms) to have any direct toxic effects on retinal ganglion cells [54,55]. Moreover, bevacizumab seems to have neutral effects on several types of retinal cell (including ganglion cells) in culture [56][57][58]. However, it should be noted that although no evidence of retinal toxicity can be observed by light microscopy, mitochondrial disruption in the inner segments of photoreceptors (detected by electron microscopy) and a high rate of apoptosis have been reported in rabbit eyes following the intravitreal administration of bevacizumab [59].…”

Comparação do efeito antiangiogênico do ranibizumab e do bevacizumab in vitro

“…(17) , por isso apresentam ligação ao mesmo epítopo do VEGF. Do ponto de vista estrutural diferem no tamanho e peso molecular, onde o peso molecular do ranibizumab (48 kDa) é aproximadamente um terço do peso molecular do bevacizumab (17)(18)(19) . A dose para uso clínico escolhida do ranibizumab intravítreo é aproximadamente um terço da dose do bevacizumab intravítreo, provavelmente para manter a razão molar entre os dois.…”

“…Apesar de a literatura mostrar resultados diferentes no que se refere à concentração dos medicamentos, ela mostra-se concordante com a razão molar acima descrita (14,18) . Uma possível explicação para esses achados incompatíveis pode ser a diferença metodológica, entre os estudos: diferentes tipos celulares e diferentes técnicas para avaliar o efeito inibitório das drogas.…”

The effects of intravitreally injected bevacizumab on the retina and retina pigment epithelium: experimental in-vivo electron microscopic study in intact versus vitrectomized eyes

“…It has the longest serum half-life when compared with the other anti-VEGF drugs (pegaptanib and ranibizumab) [4]. Although the exact half-life of bevacizumab in the eye is uncertain, the half-life of antibodies with similar molecular weight is approximately 5.6 days [16].…”

“…Bevacizumab (Avastin, Genentech Inc, San Francisco, California, USA) is a recombinant humanized monoclonal IgG1 antibody that binds all isoforms of vascular endothelial growth factor (VEGF) (VEGF110, VEGF121, VEGF145, VEGF165, VEGF183, VEGF189, and VEGF206) and works to neutralize its biological activity [1][2][3][4]. It consists of two antigen-binding regions that are named F ab and F c ; upon binding to these regions, bevacizumab interferes with the binding of VEGF to its respective receptors, thereby inhibiting its signal [5].…”