<i>In Vivo, In Vitro</i>Toxicity and<i>In Vitro</i>Angiogenic Inhibition of Sunitinib Malate

Dib, Eduardo; Maia, Maurício; Lima, Acacio de Souza; Costa, Eduardo de Freitas; Moraes-Filho, Milton N.; Rodrigues, Eduardo B; Penha, Fernando M.; Coppini, Larissa Pereira; Barros, Nilana M.T.; Sinigaglia‐Coimbra, Rita; Magalhães, Octaviano; Guerra, Tarcísio; Furlani, Bruno; Freymüller, Edna; Farah, Michel Eid

doi:10.3109/02713683.2011.635916

Cited by 20 publications

(19 citation statements)

References 28 publications

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“…In an ocular toxicity study on sunitinib, 30 the authors reported that no toxicity related to sunitinib was observed using an in vitro model of HUVEC and ARPE cell cultures after treatment with 12.5 and 25 mg/mL solutions (25-fold and 50-fold the concentrations used for topical treatment in our study). No toxicity was induced in the in vivo model of intravitreal injection after treatment with 12.5 mg/mL (1.25 mg/ 0.1 mL, 5-fold the concentration administered to the subconjunctival group in our study).…”

Section: Discussionmentioning

confidence: 64%

Inhibition of Corneal Neovascularization by Subconjunctival and Topical Bevacizumab and Sunitinib in a Rabbit Model

Byung-Yi

Young-sung

Baek

et al. 2013

Cornea

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Section: Discussionmentioning

confidence: 64%

Inhibition of Corneal Neovascularization by Subconjunctival and Topical Bevacizumab and Sunitinib in a Rabbit Model

Byung-Yi

Young-sung

Baek

et al. 2013

Cornea

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“…Moreover, in comparison with our study, they had used greater dose intervals. Dib and co-workers evaluated in vivo and in vitro toxicity of sunitinib malate, a multi-kinase inhibitor [33]. In the in vivo model, 0.1 cc of sunitinib was injected intravitreally in rabbits.…”

Section: Discussionmentioning

confidence: 99%

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

et al. 2015

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BackgroundThis two-phase experimental study was conducted to determine the maximum safe dose of intravitreal imatinib (IVI) and its inhibitory effect on a rat model of choroidal neovascularization (CNV).MethodsIn phase I, 60 rats were divided into six groups (A to F); five of which received IVI with concentrations of 330 (A), 250 (B), 165 (C), 80 (D), and 40 (E) µg/5 µl, and the control group (F) received balanced salt solution (BSS). In addition to electroretinography (ERG), routine histopathological analysis and immunohistochemistry for glial fibrillary acidic protein were performed. In phase II, CNV was induced by laser photocoagulation in 25 rats and the animals were divided into two groups. One group received the maximum safe dose of IVI, determined in phase I, and the other received intravitreal BSS. After 4 weeks, the groups were compared in terms of mean scores of fluorescein leakage in fluorescein angiography and the mean CNV areas in histopathological sections.ResultsIn phase I, ERG and the histopathological findings revealed retinal toxicity in groups A to D and A to C, respectively; therefore, a dose of 40 µg/5 µl imatinib was specified as the maximum safe dose for phase II. In phase II, late phase fluorescein leakage and the CNV areas were not significantly different between the imatinib-treated eyes and the controls (p = 0.62 and p = 0.5, respectively).ConclusionsDespite the safety of IVI with a dose of 40 µg/5 µl, no inhibitory effect on laser-induced CNV was observed. Further studies are required to investigate the possible synergistic effects of Imatinib with conventional anti-CNV drugs.

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“…Further trials with longer periods of follow-up will be necessary to address this point. In our study, doses of sunitinib malate were drastically decreased from the previous reports, mainly to minimize the ocular toxicity associated with sunitinib malate[25] and also to establish an objective comparison between the angioinhibitory effects of the bevacizumab versus the corrected values of sunitinib malate. The controversy in sunitinib malate dosage for the optimal CNV treatment is not ignorable and mandates further studies to elucidate the optimal dosage.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different doses of subconjunctival sunitinib with bevacizumab in the treatment of corneal neovascularization in experimental rats

et al. 2017

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Background:To compare the efficacy of subconjunctival administration of bevacizumab and different doses of sunitinib malate in reducing corneal neovascularization (CNV).Materials and Methods:In this experimental study, central corneal cauterization was created in the right eye of fifty male Sprague–Dawley rats. On day 1 (1 week after cauterization), rats were randomly assigned into five treatment groups. Group control (n = 10) received subconjunctival injection of 0.02 ml of base saline solution. Group 1 (n = 10) received 0.02 ml of bevacizumab (25 mg/ml). Group 2, 3, and 4 (n = 10 for each group) were treated with 0.02 ml of sunitinib malate (10, 20, and 50 μg/ml, respectively). On days 1, 7, and 14, digital photographs of the cornea were taken, and the area of CNV was measured.Results:During the 2-week follow-up, CNV area in treatment groups was less than in control group (P < 0.05). On day 7, corneal avascular area was highest in Group 3 at 63%. On day 14, the area of CNV in Groups 2 and 3 was less than in Group 1 (P = 0.031 and 0.011, respectively), but the difference between Groups 2 and 3 was not statistically significant (P = 0.552). The decreased CNV area on day 14 in Group 4 was significant in comparison to bevacizumab, but it was not significant on day 7 (P = 0.25 on day 7 and 0.002 on day 14).Conclusion:Subconjunctival sunitinib malate is more effective than bevacizumab in regressing CNV. This effect is more prominent on day 14.

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In Vivo, In VitroToxicity andIn VitroAngiogenic Inhibition of Sunitinib Malate

Abstract: Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.

Cited by 20 publications

References 28 publications

Inhibition of Corneal Neovascularization by Subconjunctival and Topical Bevacizumab and Sunitinib in a Rabbit Model

Inhibition of Corneal Neovascularization by Subconjunctival and Topical Bevacizumab and Sunitinib in a Rabbit Model

Safe dose of intravitreal imatinib and its effect on laser-induced choroidal neovascularization: a rat-model experiment

Comparison of different doses of subconjunctival sunitinib with bevacizumab in the treatment of corneal neovascularization in experimental rats

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