April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Serum levels of intravitreal ranibizumab after vitrectomy, lensectomy and non-surgical controls in a rabbit model
Author Affiliations & Notes
  • John Byron Christoforidis
    Ophthalmology & Visual Science, University of Arizona College of Medicine, Tucson, AZ
    Department of Ophthalmology, Ohio State University College of Medicine, Columbus, OH
  • Zhongfa Liu
    College of Pharmacy, Ohio State University, Columbus, OH
  • Angela Jiang
    Department of Ophthalmology, Ohio State University College of Medicine, Columbus, OH
  • Jillian Wang
    Department of Ophthalmology, Ohio State University College of Medicine, Columbus, OH
  • Zhliang Xie
    College of Pharmacy, Ohio State University, Columbus, OH
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1938. doi:
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      John Byron Christoforidis, Zhongfa Liu, Angela Jiang, Jillian Wang, Zhliang Xie; Serum levels of intravitreal ranibizumab after vitrectomy, lensectomy and non-surgical controls in a rabbit model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1938.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To determine serum levels of intravitreally-placed ranibizumab after vitrectomy and lensectomy-vitrectomy and to compare these with non-operated eyes in a rabbit model.

Methods: Five Dutch-belted rabbits underwent pars plana vitrectomy (PPV), 5 rabbits underwent pars plana lensectomy (PPL) and 5 rabbits served as non-surgical controls. Twelve days following the surgical procedures, each operated eye underwent an intravitreal injection consisting of 0.5 mg/0.05 mL ranibizumab. Serum levels from each rabbit were drawn on days 2, 4, 7, 10, 14, 21, 28 and 35 and were measured with ELISA immunoassay. The minimum detection limit of the assay for pharmacokinetic analysis of ranibizumab was 1 ng/mL, and the linear range of the assay was 1 to 500 ng/mL.

Results: All 3 groups had very low serum ranibizumab levels. The average peak serum concentration (Cmax) was highest for the control group (9.77 ± 6.00 ng/mL), and was similar between the PPV (6.86 ± 3.05 ng/mL) and PPL 6.28 ± 3.93 ng/mL). The mean time to maximal plasma concentration (Tmax) in days was earliest for the PPL group (3.00 ± 0.63), followed by the non-surgical control groups (3.33 ± 0.52) and PPV (5.33 ± 1.29) groups. The serum levels were similar in all three groups until day 4 and were only detectable among the non-surgical control subjects on days 10 and 14. After day 14 there were no detectable levels in any of the three groups. The mean half-life (T1/2) was fastest for the PPV group (0.39 ± 0.15 days) followed by the PPL (0.50 ± 0.02 days) and non-surgical control groups (0.85 ± 0.39 days).

Conclusions: Serum ranibizumab levels were very low on the order of ng/mL in all three groups following intravitreal injection and declined rapidly in both surgical groups. The half-life of ranibizumab was prolonged in non-surgical eyes compared to the surgical groups presumably due to a slower release from the vitreous cavity.

Keywords: 748 vascular endothelial growth factor • 503 drug toxicity/drug effects • 412 age-related macular degeneration  
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