微透析活体采样比较静脉和玻璃体内注射万古霉素在兔玻璃体内的通透性

Microdialysis in a conscious rabbit ocular posterior segment and the pharmacokinetics study of vancomycin after intravenous and intravitreal administration

背景:目前眼部药代动力学研究的人体及动物实验采样方法,均是在体外进行,存在诸多的弊端。目的:利用微透析活体采样技术,建立眼后节清醒动物药代动力学模型,比较静脉注射和玻璃体内注射万古霉素在兔玻璃体内的通透性。方法:纳入15只兔,制备眼内炎模型。将微透析探针植入清醒兔眼玻璃体内24h后,随机分成3组,即静脉注射组、玻璃体内注射组及静脉注射+玻璃体内注射组,分别根据不同的给药方式注射万古霉素。高效液相色谱-紫外检测法连续检测兔眼玻璃体万古霉素的浓度,3p97药代动力学软件拟合药动学参数。结果与结论:静脉注射组兔眼玻璃体内的药物浓度较低,达不到有效的治疗效果;玻璃体内注射组及静脉注射+玻璃体内注射组兔眼给药后72h,玻璃体内万古霉素的浓度均高于有效治疗浓度。提示微透析方法联合高效液相色谱-紫外检测法,可以连续、在线、活体检测清醒动物玻璃体内药物浓度;单次静脉注射万古霉素后,玻璃体内不能达到有效治疗剂量。

BACKGROUND： Currently, in the pharmacokinetic studies of the eye, the sample selection is often carried out in vitro, and there are many disadvantages. OBJECTIVE： To develop a novel ocular microdialysis technology in conscious rabbit eyes, and to compare the difference of the pharmacokinetics of vancomycin after intravenous and intravitreal administration. METHODS： Fifteen healthy and mature rabbits were used to prepare endophthalmitis models and were randomly divided into three groups （intravenous administration, intravitreal administration and intravenous＋intravitreal administration） at 24 hours after microdialysis probe was implanted. Vitreous vancomycin concentration was detected by high performance liquid chromatography-ultraviolet （HPLC-UV）. RESULTS AND CONCLUSION： The vancomycin concentration in the intravenous administration group was much lower than the other two groups. At 72 hours after administration, the vancomycin concentrations in the intravitreal administration and intravenous＋intravitreal administration groups reached a therapeutic concentration. It is indicated that microdialysis combined with HPLC-UV can continuously and in vivo detect the vancomycin concentration in the vitreous body, and single administration of vancomycin cannot reach a therapeutic concentration.