Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes.
OBJECTIVE
The aim of this study was to evaluate whether intravitreal triamcinolone hexacetonide (TH) is a safe, longer lasting alternative to intravitreal triamcinolone acetonide (TA) in the rabbit eye.


METHODS
Three groups, each comprising of 15 Dutch-belted rabbits, received a unilateral injection of 0.1 mL of drug and 0.1 mL of physiologic salt solution in the fellow eye. Group I received TA, group II received commercially available TH, and group III received reformulated iso-osmolar triamcinolone hexacetonide (rTH). Simultaneous bilateral dark-adapted electroretinography was performed following the injection. Retinal morphology was assessed by using histopathology in each group enucleated 12 weeks after injection. High-performance liquid chromatography of vitreous isolated from the enucleated eyes was used to determine drug concentrations.


RESULTS
A significant reduction in saturated a-wave and maximal scotopic b-wave was observed in the group II eyes relative to the fellow control eyes at both 2 and 12 weeks postinjection (P < 0.001 for each comparison) but not in the other groups. Histopathology showed no differences between drug-injected eyes and fellow control eyes in groups I and III, but in group II there was severe degeneration of all retina layers. In group I, the drug half-life was 17.7 +/- 1.7 days, group II 44 +/- 13 days, and group III 12.8 +/- 2.3 days.


CONCLUSIONS
The half-life of commercially available TH in the vitreous is double that of TA, but the former is toxic to the retina in this rabbit model. Reformulated iso-osmolar TH showed no evidence of deleterious effects to retina function or structure but had a similar half-life to TA.
Abd-El-Barr
Muhammad M
MM
Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA.
Albini
Thomas A
TA
Carvounis
Petros E
PE
He
Feng
F
Manzano
Roberta P A
RP
Chevez-Barrios
Patricia
P
Wensel
Theodore G
TG
Wu
Samuel M
SM
Holz
Eric R
ER
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004596:Electroretinography; D006207:Half-Life; D007267:Injections; D009994:Osmolar Concentration; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014822:Vitreous Body
D000893:Anti-Inflammatory Agents; D014222:Triamcinolone Acetonide; C005900:triamcinolone hexacetonide