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Different intravitreal properties of three triamcinolone formulations and their possible impact on retina practice.

PURPOSE
We sought to better characterize the intravitreal profile of different triamcinolone formulations.


METHODS
The study was performed in vitro and in vivo. Kenalog-40, Triesence, and Transton were characterized for ocular pharmacokinetics, particle size, crystallinity, and dissolving kinetics in vitreous following an intravitreal injection into 12 rabbit eyes. The relationship of free drug levels in the aqueous and vitreous was investigated through a dual-probe microdialysis and liquid chromatography tandem mass spectrometry.


RESULTS
Triesence had the most uniform particle size distribution (mean 11.51 μm) and Kenalog-40 had the largest particle sizes (mean 18.86 μm). Triesence and Kenalog-40 had 100% crystallinity, while Transton had 89% crystallinity. Triesence had a slower dissolution in vitreous than that of Kenalog-40, and Transton had the fastest dissolution, though their solubility was very similar. Following a 1.2 mg intravitreal injection in the rabbit eye, Triesence had a significantly lower ocular free drug level than Kenolog-40 (P = 0.025) and Transton (P = 0.007). Quantitative dual-probe microdialysis revealed that the aqueous free triamcinolone (Kenolog-40) was less than 1% of the vitreous free triamcinolone during the first few hours, and this percentage increased to 26.8% at 2 weeks and was 11.7% at 3 weeks following an intravitreal injection.


CONCLUSIONS
Triesence demonstrated a significantly slower dissolution profile and lower free drug level in the vitreous than the other preserved triamcinolone, which may translate into a longer therapeutic duration and lower rate of drug-associated complications.