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早产儿视网膜病变患儿贝伐单抗的药代动力学及其对血清 VEGF 和 IGF-1 的影响。

Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity.

机构信息

Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.

Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States.

出版信息

Invest Ophthalmol Vis Sci. 2015 Jan 22;56(2):956-61. doi: 10.1167/iovs.14-15842.

DOI:10.1167/iovs.14-15842
PMID:25613938
Abstract

PURPOSE

To measure serum levels of bevacizumab and to compare serum levels of free vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in infants who were treated with either intravitreal injection of bevacizumab (IVB) or laser for type 1 retinopathy of prematurity (ROP).

METHODS

Twenty-four infants with type 1 ROP were randomized into three treatment groups: IVB at 0.625 mg per eye per dose, IVB at 0.25 mg per eye per dose, and laser. Blood samples were collected prior to treatment and on posttreatment days 2, 14, 42, and 60. Weekly body weights were documented from birth until 60 days post treatment. Serum levels of bevacizumab, free VEGF, and IGF-1 were measured with enzyme-linked immunosorbent assay (ELISA).

RESULTS

Serum bevacizumab was detected 2 days after the injection, peaked at 14 days, and persisted for up to 60 days with half-life of 21 days. Area under the curve (AUC) analysis showed that systemic exposure to bevacizumab was variable among the subjects and was dose dependent. Serum free VEGF levels decreased in all three subgroups 2 days post treatment, with more significant reductions found in both IVB-treated groups, P = 0.0001. Serum IGF-1 levels were lower in both IVB-treated groups.

CONCLUSIONS

Clearance of bevacizumab from the bloodstream in premature infants takes at least 2 months. Although serum free VEGF levels decreased following either laser or bevacizumab treatment, the reductions were more significant in the IVB-treated groups. Potential long-term effects of systemic exposure to bevacizumab in infants need to be studied further.

摘要

目的

测量贝伐单抗的血清水平,并比较接受玻璃体内注射贝伐单抗(IVB)或激光治疗 1 型早产儿视网膜病变(ROP)的婴儿的游离血管内皮生长因子(VEGF)和胰岛素样生长因子-1(IGF-1)的血清水平。

方法

将 24 例 1 型 ROP 婴儿随机分为三组:每只眼 0.625 毫克剂量的 IVB、每只眼 0.25 毫克剂量的 IVB 和激光。在治疗前和治疗后第 2、14、42 和 60 天采集血样。从出生到治疗后 60 天,每周记录体重。采用酶联免疫吸附试验(ELISA)检测血清贝伐单抗、游离 VEGF 和 IGF-1 水平。

结果

注射后 2 天即可检测到血清贝伐单抗,14 天达到峰值,60 天内持续存在,半衰期为 21 天。曲线下面积(AUC)分析显示,受试者之间贝伐单抗的全身暴露量不同,且与剂量相关。三组中,所有婴儿在治疗后 2 天游离 VEGF 水平均下降,IVB 治疗组下降更为显著(P = 0.0001)。两组 IVB 治疗组的 IGF-1 水平均较低。

结论

早产儿血液中贝伐单抗的清除至少需要 2 个月。尽管激光或贝伐单抗治疗后血清游离 VEGF 水平下降,但 IVB 治疗组下降更为显著。需要进一步研究婴儿全身暴露于贝伐单抗的潜在长期影响。

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