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INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

Yang Y, Bailey C, Loewenstein A, Massin P - Retina (Philadelphia, Pa.) (2015)

Bottom Line: There is a relationship between visual gains and drug persistence in the intravitreal compartment.Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery.With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

View Article: PubMed Central - PubMed

Affiliation: *Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom; †University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; ‡Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and §Department of Ophthalmology, Lariboisière Hospital, Paris, France.

ABSTRACT

Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.

Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials.

Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.

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Related in: MedlinePlus

Concentration of DEX in monkey eyes.32 Republished with permission of the Association for Research in Vision and Ophthalmology, from Chang-Lin JE, et al. Invest Ophthalmol Vis Sci 2011;52:80–86; permission conveyed through Copyright Clearance Center, Inc. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
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Figure 3: Concentration of DEX in monkey eyes.32 Republished with permission of the Association for Research in Vision and Ophthalmology, from Chang-Lin JE, et al. Invest Ophthalmol Vis Sci 2011;52:80–86; permission conveyed through Copyright Clearance Center, Inc. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

Mentions: The release kinetics of DEX also were studied in 34 monkeys after bilateral implantation of 0.7 mg of sustained-release DEX implants.32 Chang-Lin et al32 showed that this bioerodible dose formulation releases with a significant burst—for approximately 2 months—before an exponential decline in release (Figure 3). After 6 months, DEX was below the limits of detection for this assay (0.001 ng/mL in the vitreous humor, 0.001 ng/mL for the retina, and 0.200 ng/mL for plasma). The difference between intravitreal injection of a bolus dose of TA and a biodegradable release form of DEX is most visible in the duration of the burst phase, during which the highest concentration of drug is released.


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

Yang Y, Bailey C, Loewenstein A, Massin P - Retina (Philadelphia, Pa.) (2015)

Concentration of DEX in monkey eyes.32 Republished with permission of the Association for Research in Vision and Ophthalmology, from Chang-Lin JE, et al. Invest Ophthalmol Vis Sci 2011;52:80–86; permission conveyed through Copyright Clearance Center, Inc. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697357&req=5

Figure 3: Concentration of DEX in monkey eyes.32 Republished with permission of the Association for Research in Vision and Ophthalmology, from Chang-Lin JE, et al. Invest Ophthalmol Vis Sci 2011;52:80–86; permission conveyed through Copyright Clearance Center, Inc. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.
Mentions: The release kinetics of DEX also were studied in 34 monkeys after bilateral implantation of 0.7 mg of sustained-release DEX implants.32 Chang-Lin et al32 showed that this bioerodible dose formulation releases with a significant burst—for approximately 2 months—before an exponential decline in release (Figure 3). After 6 months, DEX was below the limits of detection for this assay (0.001 ng/mL in the vitreous humor, 0.001 ng/mL for the retina, and 0.200 ng/mL for plasma). The difference between intravitreal injection of a bolus dose of TA and a biodegradable release form of DEX is most visible in the duration of the burst phase, during which the highest concentration of drug is released.

Bottom Line: There is a relationship between visual gains and drug persistence in the intravitreal compartment.Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery.With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

View Article: PubMed Central - PubMed

Affiliation: *Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom; †University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; ‡Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and §Department of Ophthalmology, Lariboisière Hospital, Paris, France.

ABSTRACT

Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.

Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials.

Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose.

Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.

Show MeSH
Related in: MedlinePlus