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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

Mean (±standard error of the mean) FAc concentration in the vitreous humor of rabbits.34 Asterisk indicates that a second randomized treatment was administered during Week 52.
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Figure 4: Mean (±standard error of the mean) FAc concentration in the vitreous humor of rabbits.34 Asterisk indicates that a second randomized treatment was administered during Week 52.

Mentions: The release kinetics of FAc sustained-release implants have been studied in rabbit vitreous with both the Retisert and the ILUVIEN delivery systems. The FAc-releasing Retisert implant was surgically placed into the eyes of anesthetized rabbits via sclerotomy and suture.33 Near zero–order kinetics were noted with vitreous humor levels relatively constant from the first time point (2 hours) through 1 year after implantation.33 Plasma levels were below the lower limit of quantitation (200 pg/mL for Retisert) at all times. Release kinetics of ILUVIEN FAc implants were studied in pigmented rabbits.34 After intravitreal injection of different doses of FAc implants, exposure in the vitreous humor was assessed (Figure 4). Quantifiable FAc concentrations were not observed at any dose level in the plasma (lower limit of quantitation, 100 pg/mL for ILUVIEN). The ILUVIEN delivery system and the Retisert system exhibited near zero–order release kinetic profiles but differed in intraocular exposure to FAc based on observed vitreous concentrations. The overall burst heights of corticosteroid concentration in the vitreous found with FAc implants were orders of magnitude lower than either TA or the bioerodible system releasing DEX (1–20 ng/g for FAc vs. >1100 ng/g for DEX and >10,000 ng/g for TA).


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

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

Mean (±standard error of the mean) FAc concentration in the vitreous humor of rabbits.34 Asterisk indicates that a second randomized treatment was administered during Week 52.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Mean (±standard error of the mean) FAc concentration in the vitreous humor of rabbits.34 Asterisk indicates that a second randomized treatment was administered during Week 52.
Mentions: The release kinetics of FAc sustained-release implants have been studied in rabbit vitreous with both the Retisert and the ILUVIEN delivery systems. The FAc-releasing Retisert implant was surgically placed into the eyes of anesthetized rabbits via sclerotomy and suture.33 Near zero–order kinetics were noted with vitreous humor levels relatively constant from the first time point (2 hours) through 1 year after implantation.33 Plasma levels were below the lower limit of quantitation (200 pg/mL for Retisert) at all times. Release kinetics of ILUVIEN FAc implants were studied in pigmented rabbits.34 After intravitreal injection of different doses of FAc implants, exposure in the vitreous humor was assessed (Figure 4). Quantifiable FAc concentrations were not observed at any dose level in the plasma (lower limit of quantitation, 100 pg/mL for ILUVIEN). The ILUVIEN delivery system and the Retisert system exhibited near zero–order release kinetic profiles but differed in intraocular exposure to FAc based on observed vitreous concentrations. The overall burst heights of corticosteroid concentration in the vitreous found with FAc implants were orders of magnitude lower than either TA or the bioerodible system releasing DEX (1–20 ng/g for FAc vs. >1100 ng/g for DEX and >10,000 ng/g for TA).

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