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贝伐单抗与曲安奈德玻璃体内注射联合用药的抗血管内皮生长因子活性

Anti-vascular endothelial growth factor activity in the bevacizumab and triamcinolone acetonide combination for intravitreal use.

作者信息

Giammaria Daniele, Cinque Benedetta, Di Lodovico Domenico, Savastano Maria Cristina, Cifone Maria Grazia, Spadea Leopoldo

机构信息

Department of Surgical Sciences, Eye Clinic, University of L'Aquila, L'Aquila - Italy.

出版信息

Eur J Ophthalmol. 2009 Sep-Oct;19(5):842-7. doi: 10.1177/112067210901900525.

Abstract

PURPOSE

To find out if the combination for intravitreal use of the antibody bevacizumab (AvastinTM; Genentech, Inc., San Francisco, CA) and triamcinolone acetonide (TA) (Kenacort; Bristol-Myers Squibb, Anagni, Italy) could affect over time the anti -vascular endothelial growth factor (VEGF) activity of bevacizumab.

METHODS

Two different combined preparations were obtained, drawing up together 1.25 mg/0.05 mL of bevacizumab and 2 mg/0.05 mL (B+TA(2mg)) or 4 mg/0.05 mL (B+TA(4mg)) of TA into insulin syringes with 29-G needle. Control preparations were obtained with bevacizumab and an injectable solution (B). The syringes were stored refrigerated at 4 degrees C. The bevacizumab concentration was measured, through its binding to VEGF-165 isoform, at 48 hours and at 1 week.

RESULTS

No preparations showed statistically significant changes in bevacizumab concentration with time (p=0.74 for B+T(2mg), p=0.92 for B+T(4mg), p=0.57 for B). The B+TA(2mg) preparations showed a larger percentage of degradation of bevacizumab than the B+TA(4mg) preparations (28.4% versus 17.6% at 48 hours; 26.4% versus 18% at 1 week). The B control preparations showed the lowest drug degradation: 9.6% at 48 hours and 14.8% at 1 week.

CONCLUSIONS

After storage at 4 degrees C for 48 hours and 1 week, the combined preparations showed a larger reduction in bevacizumab concentration than the control preparations. No significant change was observed with the length of storage. The preparations obtained mixing 4 mg/0.05 mL of TA and 1.25 mg/0.05 mL of bevacizumab maintained the highest anti-VEGF activity over time.

摘要

目的

探究玻璃体内联合使用抗体贝伐单抗(阿瓦斯汀;基因泰克公司,加利福尼亚州旧金山)和曲安奈德(TA)(康宁克通;百时美施贵宝公司,意大利阿纳尼)是否会随时间影响贝伐单抗的抗血管内皮生长因子(VEGF)活性。

方法

制备两种不同的联合制剂,将1.25mg/0.05mL的贝伐单抗与2mg/0.05mL(B + TA(2mg))或4mg/0.05mL(B + TA(4mg))的TA一起吸入带有29G针头的胰岛素注射器中。对照制剂由贝伐单抗和一种可注射溶液(B)制成。注射器在4℃冷藏保存。在48小时和1周时,通过贝伐单抗与VEGF - 165异构体的结合来测量其浓度。

结果

没有制剂显示贝伐单抗浓度随时间有统计学显著变化(B + T(2mg)的p = 0.74,B + T(4mg)的p = 0.92,B的p = 0.57)。B + TA(2mg)制剂中贝伐单抗的降解百分比高于B + TA(4mg)制剂(48小时时为28.4%对17.6%;1周时为26.4%对18%)。B对照制剂显示出最低的药物降解:48小时时为9.6%,1周时为14.8%。

结论

在4℃保存48小时和1周后,联合制剂中贝伐单抗浓度的降低幅度大于对照制剂。储存时间长短未观察到显著变化。混合4mg/0.05mL的TA和1.25mg/0.05mL的贝伐单抗制成的制剂随时间保持了最高的抗VEGF活性。

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