Pharmacokinetics, Pharmacodynamics, and Visual Dissolution Rates of Three Forms of Triamcinolone Acetonide (TA) in Rabbits

Abstract

Purpose: : To compare the durability of three formulations of TA including Kenalog®, Triesence® and Leiter’s compounding pharmacy preservative free TA (PFTA) in Dutch-belted rabbits using direct visualization, pharmacodynamics (PD), and pharmacokinetics (PK).

Methods: : PK experiment: Three rabbits per group (six eyes) were injected with one of three 4mg intravitreal TA formulations. Wide field imaging was serially performed to document residual drug mass. After 19 weeks, eyes were collected for PK analysis. PD experiment: Four different groups (three TA groups and one control group) received intravitreal human VEGF-165 every two weeks starting one week before TA injection then followed with imaging to assess drug mass, and fluorescein angiography (FA) to assess VEGF retinal vasculopathy as a measure of residual steroid effect. FAs were graded: level 0 no vascular changes, level 1 vessel dilation and tortuosity with minimal leakage, level 2 mild to moderate leakage, and level 3 severe leakage. All animals underwent non-aspirating vitrectomy 2-4 weeks prior to TA injection to create syneretic vitreous similar to aged human vitreous.

Results: : The remaining TA mass after 19 weeks was 12091±2512 pixels for the Kenalog® group, 5577±1477 for Triesence® , and 1535±329 for Leiter’s PFTA., Mean FA leakage at week 29 was 1±0.5 for the Kenalog®, 1.4± 0.6 for Triesence, 3±0 for Leiter’s PFTA, and 3±0 for control. Mean particle size measured for the injected lots were 47um for Kenalog, 26um for Triesense, and 22um for Leiter’s PFTA. .

Conclusions: : Kenalog appeared to have the longest durability in this study based on both observable dissolution as well as pharmacodynamics, followed by Triesence. Leiter’s PFTA appreared to have the shortest durability. TA particle size correlates with efficacy and durability suggesting that the smaller particle size formulations may be cleared faster from the syneretic vitreous.

Keywords: retina