Vitreous pharmacokinetics and retinal safety of intravitreal preserved versus non-preserved triamcinolone acetonide in rabbit eyes.
To compare the intravitreal pharmacokinetic profile of a triamcinolone acetonide formulation containing the preservative benzyl alcohol (TA-BA) versus a preservative-free triamcinolone acetonide formulation (TA-PF), and evaluate potential signs of toxicity to the retina.



A total of 60 New Zealand male white rabbits, divided into two groups, were studied. In the TA-BA group, 30 rabbits received an intravitreal injection of TA-BA (4  mg/0.1 ml) into the right eye. In the TA-PF group, 30 rabbits received an intravitreal injection of TA-PF (4  mg/0.1 ml) into the right eye. The intravitreal drug levels were determined in 25 animals from each group by high-performance liquid chromatography (HPLC). The potential for toxicity associated with the intravitreal triamcinolone injections was evaluated in five randomly selected animals from each group by electroretinography (ERG) and by light microscopy.



Median intravitreal concentrations of TA-BA (µg/ml) were 1903.1, 1213.0, 857.8, 442.0, 248.6 at 3, 7, 14, 21 and 28 days after injection. Intravitreal concentrations of TA-PF (µg/ml) were 1032.9, 570.1, 516.6, 347.9, 102.8 at 3, 7, 14, 21 and 28 days after injection. The median intravitreal triamcinolone concentration was significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection (p < 0.05). There was no significant difference between the two groups in median triamcinolone concentration at the other time points evaluated. There was no evidence of toxic effects on the retina in either group based on ERG or histological analyses.



Following a single intravitreal injection, the median concentration of triamcinolone acetonide is significantly higher in the TA-BA compared to the TA-PF group at 7 days post-injection. No toxic reactions in the retina were observed in either group.
Department of Ophthalmology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. rafaelretina@globo.com
Rafael C
RC
Oliveira
André
A
Messias
Rubens C
RC
Siqueira
Marco A
MA
Bonini-Filho
Antônio
A
Haddad
Francisco M
FM
Damico
Alfredo
A
Maia-Filho
Pedro T B
PT
Crispim
Juliana B
JB
Saliba
Jefferson A S
JA
Ribeiro
Ingrid U
IU
Scott
Armando S
AS
Cunha
Rodrigo
R
Jorge
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism*
D014222:Triamcinolone Acetonide