微透析和高效液相色谱检测万古霉素在清醒兔眼玻璃体内的浓度(英文)

背景:万古霉素玻璃体内注射后的药代动力学资料较少。目的:观察万古霉素玻璃体腔内注射后在清醒兔眼玻璃体内的浓度。方法:将微透析探针植入清醒正常兔眼和细菌性眼内炎兔眼玻璃体内24h后,向玻璃体内注射10g/L万古霉素0.1mL,利用微透析采样技术联合高效液相色谱法连续检测万古霉素注射后0.5,1,2,4,6,12,24,48,72,84h,兔眼玻璃体内的药物浓度。结果与结论:万古霉素在正常兔眼玻璃体内的代谢呈开放式二室模型,玻璃体内的峰值浓度为695.92mg/L,半衰期51.66h;在细菌性眼内炎兔眼玻璃体内的代谢呈一室模型,万古霉素的峰值浓度为713.35mg/L,半衰期为11.91h。所有动物给药84h,玻璃体内万古霉素的浓度均高于最小抑菌浓度。实验在动物清醒状态下实时、连续、动态采样,检测结果准确,能满足万古霉素药动学分析的需要。

Microdialysis and high performance liquid chromatography detection for vancomycin concentration in vitreous chamber of conscious rabbits

BACKGROUND: There are currently few studies regarding the pharmacokinetics of vancomycin via intravitreous injection. OBJECTIVE: To determine the concentration of vancomycin injected into the vitreous chamber of conscious rabbits. METHODS: A microdialysis probe was implanted into vitreous chamber of normal rabbit eyes and rabbit eyes infected with bacterial endophthalmitis for 24 hours, and 10 g/L vancomycin 0.1 mL was administered intravitreally. The drug concentration in the vitreous chamber of rabbit eyes was determined at 0.5, 1, 2, 4, 6, 12, 24, 48, 72 and 84 hours after injection, through the microdialysis and high performance liquid chromatogram-ultraviolet detection. RESULTS AND CONCLUSION: The metabolism of vancomycin showed an open two-compartment model in normal rabbit eyes. Its half-life was 51.66 hours and the peak concentration was 695.92 mg/L. The metabolism of vancomycin in the infected vitreous chamber showed a one-compartment model. Its half-life was 11.91 hours and the peak concentration was 713.35 mg/L. All rabbits were injected with drugs for 84 hours and the intravitreous concentration of vancomycin was higher than minimal inhibitory concentration. The experimental findings indicate that microdialysis coupled to high performance liquid chromatography is a powerful tool to investigate the ocular pharmacokinetics of vancomycin, and the samples are harvested in a real-time, continuous and dynamic fashion when the experimental animals are conscious.