Pharmacokinetics of Intravitreal Bevacizumab (Avastin)
Presented at: American Society of Retinal Specialists meeting, September 2006, Cannes, France; Combined Retina Society and Jules Gonin Club meeting, October 2006, Capetown, South Africa; and American Academy of Ophthalmology meeting, November 2006, Las Vegas, Nevada.
Received 29 October 2006; accepted 23 January 2007.
Purpose
To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin).
Design
Experimental animal study.
Participants
Twenty Dutch-belted rabbits.
Methods
One eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum.
Main Outcome Measures
Bevacizumab concentrations in the aqueous, vitreous, and serum.
Results
Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10μg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 μg/ml 3 days after drug administration. A maximum serum concentration of 3.3 μg/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 μg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks.
Conclusion
The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
2Department of Biochemistry, Mayo Clinic, Rochester, Minnesota.
3Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
Correspondence to Sophie J. Bakri, MD, Mayo Clinic, Department of Ophthalmology, 200 First Street SW, Rochester, MN 55905.
Manuscript no. 2006-1240.
Supported by an unrestricted grant from Research to Prevent Blindness, New York, New York.
No author has a proprietary interest in any of the products mentioned in the article.
ABSTRACT