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IVT injection of DXP emulsion

Safe and effective administration alternative

Evry – mechentel news – IVT injections of DXP emulsion are obviously a safe and effective alternative for administration of corticosteroids to treat back of the eye diseases complicated by macular edema, according to Dr. P. Daull et al. of Novagali Pharma S.A. Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT ) DXP emulsions in preclinical models. Methods: Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Results: Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to basal levels and no evidence of cataract formation. The result of the research was published in January issue 2013 oft the Journal of Ocular Pharmacology and Therapeutics. The scientists came to the conclusion that IVT injections of DXP emulsions were well tolerated and shown to be efficacious for the sustained release of the drug, with the potential to control vascular leakage up to 9 months following a single IVT injection.

Autors: Daull P, Paterson CA, Kuppermann BD, Garrigue JS. Correspondence: 1 Novagali Pharma SA , Evry,
Frankreich. Study: A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal
sustained delivery of corticosteroid for treatment of macular edema. Source: : J Ocul Pharmacol Ther.
2013 Jan 18. Web: http://online.liebertpub.com/doi/abs/10.1089/jop.2012.0044?url_ver=Z39.88-

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