Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes

Muhammad M. Abd-El-Barr, Thomas A Albini, Petros E. Carvounis, Feng He, Roberta P A Manzano, Patricia Chevez-Barrios, Theodore G. Wensel, Samuel M. Wu, Eric R. Holz

Research output: Contribution to journalArticle

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Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalJournal of Ocular Pharmacology and Therapeutics
Volume24
Issue number2
DOIs
StatePublished - Apr 1 2008

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Triamcinolone Acetonide
Rabbits
Safety
Half-Life
Retina
Pharmaceutical Preparations
Injections
Electroretinography
Poisons
triamcinolone hexacetonide
Salts
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Ophthalmology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Abd-El-Barr, M. M., Albini, T. A., Carvounis, P. E., He, F., Manzano, R. P. A., Chevez-Barrios, P., ... Holz, E. R. (2008). Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes. Journal of Ocular Pharmacology and Therapeutics, 24(2), 197-205. https://doi.org/10.1089/jop.2007.0103

Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes. / Abd-El-Barr, Muhammad M.; Albini, Thomas A; Carvounis, Petros E.; He, Feng; Manzano, Roberta P A; Chevez-Barrios, Patricia; Wensel, Theodore G.; Wu, Samuel M.; Holz, Eric R.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 24, No. 2, 01.04.2008, p. 197-205.

Research output: Contribution to journalArticle

Abd-El-Barr, MM, Albini, TA, Carvounis, PE, He, F, Manzano, RPA, Chevez-Barrios, P, Wensel, TG, Wu, SM & Holz, ER 2008, 'Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes', Journal of Ocular Pharmacology and Therapeutics, vol. 24, no. 2, pp. 197-205. https://doi.org/10.1089/jop.2007.0103
Abd-El-Barr, Muhammad M. ; Albini, Thomas A ; Carvounis, Petros E. ; He, Feng ; Manzano, Roberta P A ; Chevez-Barrios, Patricia ; Wensel, Theodore G. ; Wu, Samuel M. ; Holz, Eric R. / Safety and pharmokinetics of triamcinolone hexacetonide in rabbit eyes. In: Journal of Ocular Pharmacology and Therapeutics. 2008 ; Vol. 24, No. 2. pp. 197-205.
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AU - Albini, Thomas A

AU - Carvounis, Petros E.

AU - He, Feng

AU - Manzano, Roberta P A

AU - Chevez-Barrios, Patricia

AU - Wensel, Theodore G.

AU - Wu, Samuel M.

AU - Holz, Eric R.

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N2 - Purpose: 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.

AB - Purpose: 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.

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