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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

Triamcinolone in the vitreous and anterior chamber of rabbits after injection of 6 mg of TA.27
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Figure 2: Triamcinolone in the vitreous and anterior chamber of rabbits after injection of 6 mg of TA.27

Mentions: Similar release kinetics of IVTA in rabbits' eyes have been reported in several studies. Kaamppeter et al27 studied 18 white New Zealand rabbits, each receiving an injection of 6 mg and followed up for 8 months. The authors found that TA concentrations were significantly higher in the vitreous samples than in the anterior chamber at all time points (Figure 2). In the vitreous, the concentrations of triamcinolone were highest the first day (14,434.0 ± 10,768 μg/L), whereas in the anterior chamber, the highest concentrations were observed 3 days after injection (28.9 ± 24.5 μg/L). In both sections of the eye, triamcinolone levels followed a 2-compartment model of elimination: an exponential decrease in concentration within the first 4 weeks (burst period), followed by a steady decline over the following months (duration period). At 8 months, concentrations were 3.3 ± 1.6 μg/L in the anterior chamber and 70.7 ± 37.0 μg/L in the vitreous, approximately 200 times lower than the concentration in the burst period. In another similar study, Ye et al28 examined the pharmacokinetics of IVTA in rabbits that received 4 mg or 8 mg of IVTA and then had vitreous drug concentrations measured using high-performance liquid chromatography. They found that both doses demonstrated peak at the time of initial concentration measurement (burst period) and decreased gradually over time (duration period). Following injection of 4 mg of IVTA, a concentration of 0.0524 mg/mL was detected in the vitreous after 130 days; with 8 mg of IVTA, 0.2606 mg/mL was present at 150 days after injection. Of note, no significant differences in IOP were seen between the two dosing groups, and neither group showed any signs of retinal damage.


INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

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

Triamcinolone in the vitreous and anterior chamber of rabbits after injection of 6 mg of TA.27
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Triamcinolone in the vitreous and anterior chamber of rabbits after injection of 6 mg of TA.27
Mentions: Similar release kinetics of IVTA in rabbits' eyes have been reported in several studies. Kaamppeter et al27 studied 18 white New Zealand rabbits, each receiving an injection of 6 mg and followed up for 8 months. The authors found that TA concentrations were significantly higher in the vitreous samples than in the anterior chamber at all time points (Figure 2). In the vitreous, the concentrations of triamcinolone were highest the first day (14,434.0 ± 10,768 μg/L), whereas in the anterior chamber, the highest concentrations were observed 3 days after injection (28.9 ± 24.5 μg/L). In both sections of the eye, triamcinolone levels followed a 2-compartment model of elimination: an exponential decrease in concentration within the first 4 weeks (burst period), followed by a steady decline over the following months (duration period). At 8 months, concentrations were 3.3 ± 1.6 μg/L in the anterior chamber and 70.7 ± 37.0 μg/L in the vitreous, approximately 200 times lower than the concentration in the burst period. In another similar study, Ye et al28 examined the pharmacokinetics of IVTA in rabbits that received 4 mg or 8 mg of IVTA and then had vitreous drug concentrations measured using high-performance liquid chromatography. They found that both doses demonstrated peak at the time of initial concentration measurement (burst period) and decreased gradually over time (duration period). Following injection of 4 mg of IVTA, a concentration of 0.0524 mg/mL was detected in the vitreous after 130 days; with 8 mg of IVTA, 0.2606 mg/mL was present at 150 days after injection. Of note, no significant differences in IOP were seen between the two dosing groups, and neither group showed any signs of retinal damage.

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