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P. E. Carvounis, T. A. Albini, M. M. Abd-El-Barr, R. P. A. Manzano, F. He, T. G. Wensel, S. M. Wu, E. R. Holz; Toxicity and Pharmacokinetics of Intravitreous Triamcinolone Hexacetonide. Invest. Ophthalmol. Vis. Sci. 2007;48(13):272.
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Intra-articular triamcinolone hexacetonide (TH) has been used as longer-acting alternative to intra-articular triamcinolone acetate (TA). We were interested in evaluating whether intravitreous triamcinolone hexacetonide would be a safe and longer-lasting alternative to intravitreous triamcinolone acetonide in the rabbit eye.
Three groups of 15 Dutch-belted rabbits each received unilateral injections of study drug and 0.1 ml balanced salt solution in the fellow eye. Group I received TA (Kenalog) 4mg/0.1ml, group II received commercially-available TH (Aristospan) 2mg/0.1 ml and group III received 2mg/0.1 ml purified TH suspended in an especially formulated vehicle (89.18% saline, 10.02% water, 0.75% sodium carboxymethylcellulose and 0.04% polysorbate 80). Electroretinography was used to assess for retina toxicity while high performance liquid chromatography of vitreous isolated from enucleated eyes 2, 4, 8 and 12 weeks after injection was used to calculate drug concentrations and half-life estimates.
No toxicity was demonstrable on electroretinography in Groups I and III, however in Group II there was a significant reduction in both saturated a-wave amplitude and maximal scotopic b-wave amplitude in the injected eyes at both 2 and 12 weeks following injection (p<0.01). The half-life of intravitreous drug in group I was 17.7 ±1.7 days, in group II 44 ±13 days, and in group III 12.8 ±2.3 days.
While intravitreous commercially-available TH has a significantly longer half-life relative to intravitreous TA, it results in retina toxicity. Intravitreous TH in the reformulated vehicle did not lead to retina toxicity but had a similar pharmacokinetic profile to TA. Further study will establish whether there are differences in efficacy or adverse effect profile between the two drugs.
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