万古霉素在不同病理状态兔眼内炎模型中药代动力学研究  

A pharmacokinetic study of vancomycin injected into the vitreous of rabbit eyes with endophthalmitis in different pathological conditions

作　　者：王亚玲[1] 王洪格[1] 陆岩[2] 陈晓隆[2] 

机构地区：[1]青岛市市立医院眼科,261001 [2]中国医科大学盛京医院眼科

出　　处：《中华眼底病杂志》2011年第6期573-576,共4页Chinese Journal of Ocular Fundus Diseases

摘　　要：目的观察不同病理状态兔眼玻璃体内万古霉素的浓度和药代动力学参数。方法健康成年白化兔81只，随机分为有晶状体细菌性眼内炎组（A组）、晶状体摘除手术后细菌性眼内炎组（B组）及晶状体摘除手术后眼内炎并行玻璃体切割手术组（C组），每组27只。所有兔右眼玻璃体腔注射浓度为10mg／ml的万古霉素溶液1ml。注射后0．5、2．0、4．0、6．0、12．0、24．0、48．0、72．0、84．Oh，每组注气处死3只兔，摘取眼球，收集玻璃体样品。采用高效液相色谱法（HPLc-UV）检测各组兔眼玻璃体内万古霉素浓度。应用3p97药代动力学软件拟合并计算3组玻璃体内万古霉素的药-时曲线下面积（AUC）、清除率（cL）、半衰期（t1/2）及峰值浓度（Cmax）等药代动力学参数。结果玻璃体腔注射万古霉素后各时间点，A组万古霉素浓度均高于治疗浓度。玻璃体腔注射后0．5、2．0、4．0、6．0、12．0h，B、c组万古霉素均维持较高浓度；玻璃体腔注射后24、48h，浓度下降较快；玻璃体腔注射后72h，浓度低于最低抑菌浓度。注射后不同时间点3组万古霉素浓度比较，A组与B、C组间差异均有统计学意义（P〈0．05）；B、C组间差异无统计学意义（P〉0．05）。A、B、C组万古霉素AUc分别为15790．61、7643．94、7443．44μg／（ml·h），CL分别为0．063、0．131、0．134ml／h，t1／2分别为13．49、7．15、6．93h，Cmax分别为711．56、648．45、667．74μg／ml。A组与B、C组比较，万古霉素AuC较大（t=4．963，5．097；P〈0．01），CL较低（t=2．963，3．0g7；P〈0．05），t1／2较长（r=3．315，3．481；P〈0．01）；但Cmax无明显差异（t=1．687，1．214；P〉0．05）。结论不同病理状态兔眼玻璃体内万古霉素的浓度及其药代动力学参数均存在一定差异。Objective To observe the concentration of vancomycin and the changes of pharmacokinetic parameters in rabbit vitreous with endophthalmitis in different pathological conditions. Methods Eighty-one adult healthy rabbits were randomly divided into endophthalmitis with lens group （group A）, aphakic endophthalmitis group （group B）, aphakic endophthalmitis and vitrectomy group （group C）, 27 rabbits in each group. The right eyes of all rabbits received intravitreal injection of 1 ml （10 mg/ml） vancomycin. Three rabbits from each group were sacrificed at 0.5, 2.0, 4.0, 6.0, 12.0, 24.0, 48.0, 72.0, 84.0 hours after the injection. The eyes were harvested to collect the vitreous. The vitreous concentrations of vancomycin in all the groups were detected by high performance liquid chromatography （HPLC-UV）. The pharmacokinetic parameters including the area under the curve （AUC） of the concentration-time graph, clearance rate （CL）, half-life period （t1/2） and peak concentration （Cmax） were calculated by 3p 97 pharmacokinetic software. Results The concentrations of vancomycin in the group A were always higher than the therapeutic drug levels after injection. In the group B and C, the concentrations of vancomycin remained significantly high at 0.5, 2.0, 4.0, 6.0 and 12.0 hours after injection, decreased quickly at 24 and 48 hours after injection, below the minimal inhibitory concentrations at 72 hours after injection. The differences were statistically significant among group A, B and C （t=4. 968, 5. 232; P〈0.05）, but not statistically significant between group B and C （t=1. 279, P〉0.05）. The AUC were 15 790.61, 7643.94, 7443.44 μg/（ml·h）, CL were 0. 063, 0. 131, 0. 134 ml/h, t1/2 were 13.49, 7.15, 6.93 hours and Cmax were 711.56, 648.45, 667.74 μg/ml in the group A, B and C, respectively. In the group A, the CL was lower （t=2.963, 3.097; P〈0.05） and tl/2 was longer （t=3.315, 3.481; P〈0.01） than those in the group B and C, but there was no significant difference o

关 键 词：眼内炎/药物疗法 万古霉素/投药和剂量 药代动力学 疾病模型 动物 

分 类 号：R965[医药卫生—药理学]