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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 human aqueous concentrations of FAc implants.37
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Figure 6: Mean human aqueous concentrations of FAc implants.37

Mentions: The pharmacokinetics of FAc in human aqueous was examined in the Fluocinolone Acetonide in Human Aqueous study, which compared the levels of FAc released in patients with DME receiving the ILUVIEN delivery system.14 In this study, 37 patients with DMO and 7 with uveitis had aqueous levels of FAc measured after receiving either a 0.2 µg/day insert or a 0.5 µg/day insert. Follow-up assessments were done at 1 week after treatment and then again at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months. A companion study assessed the aqueous levels of FAc associated with Retisert in patients with noninfectious posterior uveitis.37 Overall, results were similar to what was seen in the rabbit studies, with the highest burst obtained with the Retisert implant (Figure 6).37 The 0.5-μg/day FAc implant had a higher mean burst than the 0.2-μg/day ILUVIEN implant. The initial release was followed by a relatively flat profile of release, with a similar submicrogram dose released during the follow-up period for the two doses studied with the ILUVIEN system. Through Month 24, the 0.5-μg/day implant released at a slightly higher level than the 0.2-μg/day implant. The 0.2-μg/day implant continued to release FAc through 36 months (end of follow-up). Both Retisert and ILUVIEN were below the lower limit of quantitation in plasma (200 pg/mL and 100 pg/mL, respectively).23,37 The observed pharmacokinetic properties of various formulations of these corticosteroids are presented in Table 1.


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

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

Mean human aqueous concentrations of FAc implants.37
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Mean human aqueous concentrations of FAc implants.37
Mentions: The pharmacokinetics of FAc in human aqueous was examined in the Fluocinolone Acetonide in Human Aqueous study, which compared the levels of FAc released in patients with DME receiving the ILUVIEN delivery system.14 In this study, 37 patients with DMO and 7 with uveitis had aqueous levels of FAc measured after receiving either a 0.2 µg/day insert or a 0.5 µg/day insert. Follow-up assessments were done at 1 week after treatment and then again at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months. A companion study assessed the aqueous levels of FAc associated with Retisert in patients with noninfectious posterior uveitis.37 Overall, results were similar to what was seen in the rabbit studies, with the highest burst obtained with the Retisert implant (Figure 6).37 The 0.5-μg/day FAc implant had a higher mean burst than the 0.2-μg/day ILUVIEN implant. The initial release was followed by a relatively flat profile of release, with a similar submicrogram dose released during the follow-up period for the two doses studied with the ILUVIEN system. Through Month 24, the 0.5-μg/day implant released at a slightly higher level than the 0.2-μg/day implant. The 0.2-μg/day implant continued to release FAc through 36 months (end of follow-up). Both Retisert and ILUVIEN were below the lower limit of quantitation in plasma (200 pg/mL and 100 pg/mL, respectively).23,37 The observed pharmacokinetic properties of various formulations of these corticosteroids are presented in Table 1.

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