摘要
目的观察混合给药后的配伍安全以及豚鼠ABR检测和细胞形态学的变化。方法混合2种药物后,进行灯检,pH值、旋光度检测,两种药物均为临床使用剂量,观察两种药物在临床使用剂量下混合给药的安全性和有效性。健康杂色雄性豚鼠随机分为3组,GM组、GM+Aspirin-DL-Lysine组、对照组,采用听性脑干反应(ABR)、耳蜗铺片观察用药前后听阈及耳蜗毛细胞形态学改变,并检测庆大霉素血药浓度。结果混合后药物的pH值、颜色、及澄明度均无变化,混合试液与单纯药物溶液之间的旋光度无明显差异。①GM组不同频率下的ABR阈移分别为:1kHz15～18dB,8kHz17～20dB,GM+Aspirin-DL-Lysine组的阈移分别为:1kHz9～15dB,8kHz10～15dB。两组间差异显著(P<0.05);②耳蜗铺片结果显示:耳蜗铺片GM组底圈毛细胞有损伤,与正常组比较排列不整齐,毛细胞损伤向上逐渐减轻,提示与听阈升高的程度相平行。而GM+As-pirin-DL-Lysine组的毛细胞排列整齐,无损伤。结论赖氨匹林(来比林)与庆大霉素可以安全的配伍使用。单独注射正常量庆大霉素4周使豚鼠的高频ABR升高,混合注射GM+Aspirin-DL-Lysine后对豚鼠的ABR影响不明显。注射正常量庆大霉素使豚鼠耳蜗毛细胞有损伤,底圈比顶圈重,与正常组比较,毛细胞排列紊乱。而配伍使用GM+Aspirin-DL-Lysine可以减轻庆大霉素对毛细胞的损伤。与正常组比较无明显差别。
OBJECTIVE To study the prevention of gentamicin（GM） ototoxicity by Aspirin-DL-Lysine in guinea pig and the safety of compatibility of GM and LAP.METHODS The mixture color,optical rotation and sediments separately were observed under the temperature of 25 ℃ and 37 ℃.Auditory brainstem response and cochlear preparation transmission electron microscope were used to evaluate effects of hair cell on hearing threshold and morphology of hair cell.Serum levels of GM were also tested.RESULTS No change in color and no sediment occurred under the temperature of 25 ℃ and 37 ℃.Also no obvious difference was seen on the pH value under the two different temperatures.No obvious difference of optical rotation was seen between the mixture and single compound.GM group developed a progressive threshold shift.Injury in high frequency was significantly more sever than that in low frequency（P〈0.05）.Hearing loss of high frequency was heavier than that of low frequency.Thresholds of control group and Aspirin-DL-Lysine group maintained steady.Morphological results were consistent with functional changes.The worst damages occurred in the basal circles.Damages in upper circles were lighter.CONCLUSION These results suggest that Aspirin-DL-Lysine may be a promising therapeutic agent for gentamicin ototoxicity.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2008年第7期511-513,共3页
Chinese Pharmaceutical Journal
关键词
庆大霉素
耳毒性
赖氨匹林
配伍
保护作用
gentamicin
Aspirin-DL-Lysine
compatibility
ototoxicity
protect
