Pharmacokinetics of intravitreal ranibizumab (Lucentis).
OBJECTIVE
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.


METHODS
Experimental animal study.


METHODS
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.


METHODS
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 microg/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 microg/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.


CONCLUSIONS
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.
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. sbakri@hotmail.com
Sophie J
SJ
Bakri
Melissa R
MR
Snyder
Joel M
JM
Reid
Jose S
JS
Pulido
Mohamed K
MK
Ezzat
Ravinder J
RJ
Singh
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D001682:Biological Availability; D006207:Half-Life; D008297:Male; D011817:Rabbits; D000069579:Ranibizumab; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab