Ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade.
OBJECTIVE
We characterized the ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade.


METHODS
A total of 18 pigmented rabbits underwent vitrectomy and silicone oil tamponade before an intra-silicone oil injection of 1.25 mg bevacizumab. At post-injection days 1, 7, 14, 28, 42, and 56, 3 rabbits were sacrificed and enucleated, and bevacizumab concentrations were measured in various ocular tissues and plasma.


RESULTS
The bevacizumab peak concentration was reached at day 14 in the aqueous humor (4030.70 ng/mL), retina (42,171.7 ng/g), and choroid (56,243.33 ng/g). In the iris/ciliary body and plasma, the peak concentration was reached at day 7 with 52,648.30 ng/g and 197.70 ng/mL, respectively. The choroid had the maximum exposure to bevacizumab with an area under the curve calculated from time zero to the last observed time (AUC(last)) of 1,151,633.40 ng/day/g and the aqueous humor had the minimum exposure (AUC(last) = 74,611.28 ng/day/g) among the ocular tissues, while the drug exposure to the plasma was the smallest of all tissues studied (AUC(last) = 3795.17 ng/day/g). The terminal half-lives and the mean residence time of bevacizumab in the ocular tissues ranged from 3-5 and 10-13 days, respectively.


CONCLUSIONS
The peak concentration of bevacizumab in various ocular tissues and plasma was delayed and lower than that found in normal rabbit eyes; however, the terminal half-lives were similar to those found in the eyes with native vitreous following an intravitreal injection. Oil may have impacted the distribution of bevacizumab and led to an altered profile of drug level in the ocular tissues.
Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical College, Zhejiang, China.
Yu
Y
Xu
Yongsheng
Y
You
Wennan
W
Du
Chunhui
C
Zhao
Jie
J
Li
Jianbo
J
Mao
Hao
H
Chen
Lingyun
L
Cheng
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D004797:Enzyme-Linked Immunosorbent Assay; D005123:Eye / Q000378:metabolism*; D056965:Injections, Intraocular; D007429:Intraocular Pressure / Q000187:drug effects; D011817:Rabbits; D012827:Silicone Oils / Q000494:pharmacology; D014821:Vitrectomy
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D012827:Silicone Oils; D000068258:Bevacizumab