妥布霉素注射剂雾化吸入对呼吸道纤毛的毒性研究  

Respiratory ciliary toxicity study of tobramycin injection administrated by nebulization

作　　者：郭卓瑶 梅丽 纪梁缘 钱莉玲 GUO Zhuo-yao;MEI Li;JI Liang-yuan;QIAN Li-ling(Department of Respiration,Children's Hospital of Fudan University,Shanghai 201102,China;Guangzhou Institute of Respiratory Health,Guangzhou 510120,Guangdong Province,China;School of Pharmacy,East China Universityof Science and Technology,Shanghai 200237,China)

机构地区：[1]复旦大学附属儿科医院呼吸科,上海201102 [2]广州呼吸健康研究院,广东广州510120 [3]华东理工大学药学院,上海200237

出　　处：《中国临床药理学杂志》2023年第12期1679-1683,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 探讨妥布霉素注射液雾化吸入对呼吸道纤毛的毒性影响。方法 以人鼻黏膜纤毛和牛蛙上颚黏膜纤毛为研究对象,实验分为空白对照组(0.9%NaCl)、阳性对照组(1%去氧胆酸钠)、注射液实验组(硫酸妥布霉素注射液)和吸入溶液实验组(妥布霉素吸入溶液)。比较给药前后纤毛持续运动时间(PVD)和纤毛持续运动时间百分比(PPV),评价各组纤毛毒性差异。采用牛蛙上颚黏膜纤毛进一步研究妥布霉素注射液中所含辅料[苯酚、亚硫酸氢钠和乙二胺四乙酸二钠(EDTA-2Na)]的纤毛毒性。结果 人鼻黏膜纤毛实验空白对照组、阳性对照组、注射液实验组和吸入溶液实验组的PVD分别为(472.33±37.56)、0、(8.00±1.10)和(112.00±36.55)min;PPV分别为100%、0、(1.69±0.23)%和(23.71±7.74)%。注射液实验组与空白对照组、吸入溶液实验组比较,差异均有统计学意义(均P<0.05)。牛蛙上颚黏膜纤毛实验空白对照组、阳性对照组、注射液实验组和吸入溶液实验组的PVD分别为(614.67±23.30)、(51.67±10.60)、(311.50±62.03)和(430.17±40.32)min;PPV分别为100%、(8.41±1.72)%、(50.68±10.09)%和(69.98±6.56)%。注射液实验组与空白对照组、吸入溶液实验组比较,差异均有统计学意义(均P<0.05)。牛蛙上颚黏膜纤毛实验空白对照组、苯酚组、亚硫酸氢钠组和EDTA-2Na组的PVD分别为(614.67±23.30)、(140.67±24.62)、(417.83±74.62)和(601.17±27.07)min;PPV分别为100%、(22.89±4.01)%、(67.98±12.14)%和(97.80±4.40)%。苯酚组与空白对照组、亚硫酸氢钠组比较,亚硫酸氢钠组与空白对照组比较,差异均有统计学意义(均P<0.05)。结论 相比吸入溶液,抗生素注射剂存在较高的纤毛毒性,系由于其处方中防腐剂苯酚、抗氧剂亚硫酸氢钠具有不同程度的纤毛毒性。雾化吸入使用时需谨慎评估其风险获益。Objective To investigate the respiratory ciliary toxicity of tobramycin injection administrated by nebulization.Methods The nasal mucosa cilia of human and the maxillary mucosa cilia of bullfrog were used as the studying object.The experiment was divided into blank control group(0.9%NaCl),positive control group(1%sodium deoxycholate),injection group(tobramycin sulfate injection))and inhalation solution group(tobramycin inhalation solution).The differences in ciliary toxicity between groups were evaluated by comparing the persistent vibration duration(PVD),the percentage of persistent vibration(PPV)and other indicators before and after dosing.The ciliary toxicity of excipients[phenol,sodium bisulfite and ethylenediaminetetracetic acid disodium salt(EDTA-2Na)] contained in tobramycin injection was further investigated by bullfrog maxillary mucosal cilia.Results In human nasal mucosal cilia,the PVDs of blank control group,positive control group,injection group and inhalation solution group were(472.33±37.56),0,(8.00±1.10)and(112.00±36.55)min,respectively;the PPVs were 100%,0,(1.69±0.23)%and(23.71±7.74)%,respectively.There were statistically significant differences between injection group and blank control group,inhalation solution group(all P<0.05).In bullfrog maxilary cilia,the PVDs of the above four groups were(614.67±23.30),(51.67±10.60),(311.50±62.03)and(430.17±40.32)min,respectively;the PPVs were 100%,(8.41±1.72)%,(50.68±10.09)%and(69.98±6.56)%,respectively.There were statistically significant differences between injection group and blank control group,inhalation solution group(all P<0.05).In bullfrog maxillary cilia,the PVDs of the blank control group,phenol group,sodium bisulfite group and EDTA-2Na group were(614.67±23.30),(140.67±24.62),(417.83±74.62)and(601.17±27.07)min,respectively;the PPVs were 100%,(22.89±4.01)%,(67.98±12.14)%and(97.80±4.40)%,respectively.There were statistically significant differences in the above indicators between phenol group and the blank control group,sodium bis

关 键 词：妥布霉素注射液 雾化吸入 呼吸道纤毛毒性 苯酚 亚硫酸氢钠 临床用药安全 

分 类 号：R978.1[医药卫生—药品]