Elsevier

Ophthalmology

Volume 114, Issue 12, December 2007, Pages 2179-2182
Ophthalmology

Original article
Pharmacokinetics of Intravitreal Ranibizumab (Lucentis)

Presented in part at: Bascom Palmer Eye Institute Angiogenesis Meeting, February 2007, Key Biscayne, Florida.
https://doi.org/10.1016/j.ophtha.2007.09.012Get rights and content

Purpose

To describe the pharmacokinetics of 0.5 mg of intravitreal ranibizumab (Lucentis) and to compare it with that of 1.25 mg of intravitreal bevacizumab (Avastin), using the same rabbit model.

Design

Experimental animal study.

Participants

Twenty-eight Dutch-belted rabbits.

Methods

One eye of each of 20 rabbits was injected with 0.5 mg of intravitreal ranibizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Ranibizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. A further 8 rabbits were used to measure serum and fellow ranibizumab at additional time points of 3 and 8 hours.

Main Outcome Measures

Ranibizumab concentrations in the aqueous, vitreous, and serum.

Results

Although vitreous concentrations of ranibizumab declined in a monoexponential fashion with a half-life of 2.88 days, concentrations of >0.1 μg/ml ranibizumab were maintained in the vitreous humor for 29 days. Ranibizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 17.9 μg/ml, 3 days after drug administration. Elimination of ranibizumab from the aqueous humor paralleled that found in the vitreous humor, with a half-life value of 2.84 days. No ranibizumab was detected in the serum or the fellow eye.

Conclusion

In the rabbit, the vitreous half-life of 0.5-mg intravitreal ranibizumab is 2.88 days, shorter than the half-life of 1.25-mg intravitreal bevacizumab of 4.32 days. No ranibizumab was detected in the serum or the fellow uninjected eye; whereas small amounts of intravitreal bevacizumab have been detected in the serum and fellow uninjected eye.

Section snippets

Materials and Methods

Approval was obtained from the Institutional Animal Care and Use Committee at the Mayo Clinic, and the procedures adhered to the guidelines from the Association for Research in Vision and Ophthalmology for animal use in research. Twenty Dutch-belted male rabbits weighing 1.7 to 2 kg (Harlan Laboratories, Indianapolis, IN) were anesthetized with 35 mg/kg of intramuscular ketamine hydrochloride (Fort Dodge Inc., Fort Dodge, IN), 5 mg/kg of intramuscular xylazine hydrochloride (Phoenix Scientific

Results

Data were obtained from the 48 eyes of 28 rabbits. No adverse events were noted, and there were no signs of ocular inflammation.

The sensitivity of the assay was 0.375 ng/ml. The change in concentration over time for ranibizumab in vitreous and aqueous humor, both from the injected eye, is illustrated in Figure 1. A peak concentration of 162 μg/ml was achieved in the vitreous humor 1 day after intravitreal injection of 0.5 mg of ranibizumab. Vitreous concentrations of ranibizumab declined in a

Discussion

In a previous pharmacokinetic study,12 both eyes of a monkey were injected with 0.5 mg of intravitreal ranibizumab. The half-life of 0.5 mg of ranibizumab was 2.6 days in the vitreous cavity in this monkey model, which is comparable with our half-life of 2.88 days in the rabbit. The maximum serum concentration attained in the monkey was 150 ng/ml, but this was after bilateral intravitreal injection. Therefore, no data were obtained on ocular concentrations in the fellow eye. Maximum

References (15)

  • S.J. Bakri et al.

    Pharmacokinetics of intravitreal bevacizumab

    Ophthalmology

    (2007)
  • P.J. Rosenfeld et al.

    Ranibizumab for neovascular age-related macular degeneration

    N Engl J Med

    (2006)
  • D.M. Brown et al.

    Ranibizumab versus verteporfin for neovascular age-related macular degeneration

    N Engl J Med

    (2006)
  • P.J. Rosenfeld et al.

    Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration

    Ophthalmic Surg Lasers Imaging

    (2005)
  • R.M. Rich et al.

    Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration

    Retina

    (2006)
  • R.F. Spaide et al.

    Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration

    Retina

    (2006)
  • P.J. Rosenfeld et al.

    Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for macular edema from central retinal vein occlusion

    Ophthalmic Surg Lasers Imaging

    (2005)
There are more references available in the full text version of this article.

Cited by (0)

Manuscript no. 2007-820.

Supported by an unrestricted grant from Research to Prevent Blindness, New York, New York.

No author has any proprietary interest in any of the products mentioned in the article. No conflicting interest exists for any author.

View full text