Testing intravitreal toxicity of rapamycin in rabbit eyes

Manzano, Roberta Pereira de Almeida; Peyman, Gholam A.; Khan, Palwasha; Kivilcim, Muhamet; Chévez-Barrios, Patricia; Takahashi, Walter Yukihiko

doi:10.1590/s0004-27492009000100004

Cited by 22 publications

(18 citation statements)

References 26 publications

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“…These findings are consistent with the tolerability seen in another study that investigated potential retinal toxicity. 20 In Manzano's study, New Zealand albino rabbits received IVT doses of 20, 50, 200, and 1000 mg sirolimus. They performed slit-lamp and fundoscopic exams, and animals were observed for 2 weeks post IVT injection.…”

Section: Discussionmentioning

confidence: 99%

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Tolerability and Pharmacokinetics of Intravitreal Sirolimus

Mudumba

Bezwada

Takanaga

et al. 2012

Journal of Ocular Pharmacology and Therapeutics

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Sustained i.v.t. delivery was achieved in a dose-dependent fashion after the i.v.t. injection of a proprietary sirolimus depot-forming ocular formulation. Across the tolerability and safety studies, no significant findings were observed for systemic and ocular tolerability. The human WB levels were well below the daily trough systemic blood level range required for systemic immunosuppression. An i.v.t. injection of sirolimus has a PK and safety profile that is favorable for treating inflammatory conditions of the eye, such as non-infectious uveitis, and warrants further investigation in humans.

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Section: Discussionmentioning

confidence: 99%

“…Follow-up ERGs showed some decrease in amplitude in the 50, 200, and 1000 mg, but this decrease was not dose related. In addition to this study, 20 we conducted preliminary toxicity studies in rabbits using IVT doses of approximately 880 mg; sirolimus appeared to be well tolerated.…”

Section: Discussionmentioning

confidence: 99%

Tolerability and Pharmacokinetics of Intravitreal Sirolimus

Mudumba

Bezwada

Takanaga

et al. 2012

Journal of Ocular Pharmacology and Therapeutics

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“…However, multiple gastrointestinal and dermatological side effects have been observed [45]. Subsequent experimental intravitreal applications of sirolimus were well tolerated and nontoxic to the retina [46]. Phase I/II studies using different dosages are currently underway and will highlight the effectiveness and safety of intravitreal sirolimus in CNIU [47].…”

Section: Intravitreal Methotrexate Injectionmentioning

confidence: 99%

Think Global – Act Local: Intravitreal Drug Delivery Systems in Chronic Noninfectious Uveitis

Hazırolan

Pleyer

2012

Ophthalmic Res

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The eye is probably the most attractive site of the body for treatment using locally delivered therapeutic agents. An ideal indication for such an approach is noninfectious posterior uveitis. Since intraocular structures of the posterior segment are difficult to reach and are otherwise accessible only by systemic treatment, current interest is focused on the pros and cons of intravitreal drug delivery. Because of its chronic and recurrent nature, the long-term release of anti-inflammatory agents is a major treatment goal. Intravitreal injections, intravitreal implants and biodegradable devices are the most commonly used and approved approaches to deliver various agents to the vitreous. Because of their broad and potent effects, corticosteroids (CS) have been the first-line candidates for intraocular delivery. An increasing spectrum of CS preparations including nondegradable and biodegradable devices is currently available. Since repeated and long-term applications bear the risk of steroid-related complications such as increased intraocular pressure and cataract, alternative agents are currently being tested. Intravitreal injection of methotrexate, anti-VEGF (vascular endothelial growth factor), anti-TNFα (tumor necrosis factor α) and sirolimus have also been applied in patients with conflicting results. Intravitreal treatment has significantly reduced the incidence of adverse effects compared to systemic application, but due to greater ocular side effects there are still some limitations.

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“…The use of experimental models is important as there are many difficulties involved in getting intraocular tissue from patients' eyes, including technical and ethical issues. Experimental models are important for the development of new therapeutic agents as they are useful to evaluate the efficacy and toxicity of systemic and intravitreous drug delivery, such as antibiotics (3)(4)(5) , corticosteroids (6,7) , immunosuppressive drugs (8,9) , and more recently anti-VEGF (10,11) , and biological agents (e.g., tacrolimus, sirolimus, etanercept, infliximab, adalimumab, and rituximab) (12)(13)(14)(15)(16)(17)(18)(19) . The aim of this paper is to review the most used experimental autoimmune ocular inflammatory diseases models used in Ophthalmology and their most important aspects.…”

Section: Introductionmentioning

confidence: 99%