Assessment of the differences in pharmacokinetics and pharmacodynamics between four distinct formulations of triamcinolone acetonide

• Published in: Retina (Philadelphia, Pa.) Vol. 33; no. 3; p. 522
• Main Authors: Zacharias, Leandro C, Lin, Ton, Migon, Rafael, Ghosn, Corine, Orilla, Werhner, Feldmann, Barbara, Ruiz, Guadalupe, Li, Yong, Burke, James, Kuppermann, Baruch D
• Format: Journal Article
• Language: English
• Published: United States 01.03.2013
• Subjects: Animals; Biological Availability; Drug Compounding; Fluorescein Angiography; Glucocorticoids - chemistry; Glucocorticoids - pharmacokinetics; Glucocorticoids - pharmacology; Half-Life; Intravitreal Injections; Particle Size; Preservatives, Pharmaceutical; Rabbits; Recombinant Proteins; Retinal Neovascularization - chemically induced; Retinal Neovascularization - metabolism; Retinal Neovascularization - prevention & control; Solubility; Triamcinolone Acetonide - chemistry; Triamcinolone Acetonide - pharmacokinetics; Triamcinolone Acetonide - pharmacology; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - toxicity; Vitreous Body - metabolism
• ISSN: 1539-2864
• DOI: 10.1097/IAE.0b013e3182647f69

To compare the durability of Kenalog, Trivaris, Triesence, and compounding pharmacy preservative-free triamcinolone acetonide in pigmented rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and pharmacokinetics. Twenty-five Dutch-belted rabbits were used. Pharmacokinetic experiment: Rabbits were intravitreally injected with one of four 4-mg triamcinolone acetonide formulations. Wide-field imaging was serially performed to document residual drug mass. Pharmacodynamics experiment: Four triamcinolone acetonide groups and one control group received intravitreal recombinant human vascular endothelial growth factor 165 every 2 weeks and were followed with fluorescein angiography to assess vascular endothelial growth factor retinal vasculopathy as a measure of residual steroid effect. Particle size of the formulations was measured with Mastersizer 2000. Remaining triamcinolone acetonide mass after 19 weeks: 12,091 ± 2,512 pixels for the Kenalog group, 1,307.36 ± 695.57 for Trivaris, 5577 ± 1477 for Triesence, and 1,535 ± 329 for compounded preservative-free triamcinolone acetonide. Kenalog suppressed recombinant human vascular endothelial growth factor-induced retinopathy more effectively than the other triamcinolone acetonide groups at Week 39, the final time point assessed. Particle size (90th percentile) was 47 μm for Kenalog, 26 μm for Triesence, and 22 μm for both compounded preservative-free triamcinolone acetonide and Trivaris. Triamcinolone acetonide formulations do not have the same pharmacokinetics/pharmacodynamics. Kenalog has the longest vitreous visibility and durability. Particle size appears to correlate with efficacy and durability.