Pharmacokinetics of Bevacizumab after Topical, Subconjunctival, and Intravitreal Administration in Rabbits
Pharmacokinetics of Bevacizumab after Topical, Subconjunctival, and Intravitreal Administration in Rabbits
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DOI：
10.1167/iovs.08-3148
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发表时间：
2009-10-01
影响因子：
4.4
通讯作者：
Baba, Tetsuya
中科院分区：
文献类型：
--
作者：
Nomoto, Hiroyuki;Shiraga, Fumio;Baba, Tetsuya
目的。研究贝伐单抗三种不同给药途径：玻璃体内注射、结膜下注射和滴眼液在家兔体内的药代动力学。染色兔通过局部滴眼液（1.25 mg/0.05 mL，每日6次，前7天）、单次结膜下注射（1.25 mg/0.05 mL）或单次玻璃体内注射（1.25 mg/0.05 mL）在一只眼内注射贝伐单抗。在给药后1周、2周、4周和12周，采用三明治酶联免疫吸附法测定治疗组和对照组血浆和眼组织中的贝伐单抗浓度。治疗眼玻璃体内注射贝伐单抗后，虹膜/睫状体和视网膜/脉络膜的平均最大浓度（C-max）分别为109,192.6和93,990.0 ng/g，结膜下注射贝伐单抗后，C-max分别为1418.7和295.8 ng/g。在其他眼中，玻璃体腔注射时，虹膜/睫状体的C-max为753.6 ng/g，视网膜/脉络膜的C-max为224.2 ng/g，结膜下注射时，C-max分别为1192.9和187.0 ng/g。使用滴眼液时，仅在虹膜/睫状体和视网膜/脉络膜中检测到少量贝伐单抗。通过玻璃体内注射或结膜下注射给药，全身暴露于贝伐单抗的水平相同。玻璃体内注射贝伐单抗是眼内组织最有效的给药途径。此外，结膜下注射的贝伐单抗以有效水平转运到治疗眼睛的眼内组织。玻璃体内和结膜下注射贝伐单抗均导致高血浆浓度。贝伐单抗通过体循环分布到眼内组织。这种治疗可能对阻断血管内皮生长因子活性有效。（Invest Ophthalmol Vis Sci. 2009;50:4807-4813） DOI: 10.1167/iovs.08-3148
PURPOSE. To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops.METHODS. Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzyme-linked immunosorbent assay at 1, 2, 4, and 12 weeks after administration.RESULTS. After intravitreal injection in the treated eye, the mean maximum concentrations (C-max) of bevacizumab in the iris/ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the C-max was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the C-max was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection.CONCLUSIONS. Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity. (Invest Ophthalmol Vis Sci. 2009;50:4807-4813) DOI: 10.1167/iovs.08-3148