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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

Central macular thickness curves calculated from four individual CMT values after a single injection of IVTA.36
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Figure 5: Central macular thickness curves calculated from four individual CMT values after a single injection of IVTA.36

Mentions: A small study examined the release kinetics of a single injection of 4 mg of IVTA in human eyes (N = 5).35 They determined from aqueous humor samples that the pharmacokinetics followed a 2-compartment model and the half-life ranged from 76 hours to 635 hours. The mean elimination half-life was 18.6 days in nonvitrectomized eyes, suggesting that measurable concentrations of triamcinolone would be expected to last for approximately 3 months (93 ± 28 days). Audren et al36 examined the pharmacokinetics of IVTA in a larger group of patients with diffuse DME (51 injections in 37 eyes). In this study, they used population pharmacokinetic–pharmacodynamic modeling without triamcinolone concentration measurements. They found that the pharmacokinetic profile of the effect of triamcinolone on central macular thickness (CMT) was characterized by a curve in 3 phases: a fast decrease, a steady state, and a relapse (Figure 5). Similar to results of the smaller study, the mean estimated half-life of triamcinolone ± standard deviation (SD) was 15.4 ± 1.9 days. The mean (±SD) maximum duration of the effect of a single injection was 140 ± 17 days, slightly longer than previously observed. They suggested that the difference could be because of the interval between the elimination of TA and cessation of its pharmacologic activity, which is typical of corticosteroid agents. The authors further suggest that functional measurements such as mean CMT may be even more useful in the clinical field than measuring the TA concentration because this measurement reflects both the concentration and activity of TA.


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

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

Central macular thickness curves calculated from four individual CMT values after a single injection of IVTA.36
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Central macular thickness curves calculated from four individual CMT values after a single injection of IVTA.36
Mentions: A small study examined the release kinetics of a single injection of 4 mg of IVTA in human eyes (N = 5).35 They determined from aqueous humor samples that the pharmacokinetics followed a 2-compartment model and the half-life ranged from 76 hours to 635 hours. The mean elimination half-life was 18.6 days in nonvitrectomized eyes, suggesting that measurable concentrations of triamcinolone would be expected to last for approximately 3 months (93 ± 28 days). Audren et al36 examined the pharmacokinetics of IVTA in a larger group of patients with diffuse DME (51 injections in 37 eyes). In this study, they used population pharmacokinetic–pharmacodynamic modeling without triamcinolone concentration measurements. They found that the pharmacokinetic profile of the effect of triamcinolone on central macular thickness (CMT) was characterized by a curve in 3 phases: a fast decrease, a steady state, and a relapse (Figure 5). Similar to results of the smaller study, the mean estimated half-life of triamcinolone ± standard deviation (SD) was 15.4 ± 1.9 days. The mean (±SD) maximum duration of the effect of a single injection was 140 ± 17 days, slightly longer than previously observed. They suggested that the difference could be because of the interval between the elimination of TA and cessation of its pharmacologic activity, which is typical of corticosteroid agents. The authors further suggest that functional measurements such as mean CMT may be even more useful in the clinical field than measuring the TA concentration because this measurement reflects both the concentration and activity of 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