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研究盐酸曲马多在小鼠大脑额叶皮质细胞外液中的药动学,探讨靶器官药动学研究方法。小鼠麻醉后,将微透析探针植入其额叶皮质,以2μL.min 1速率向探针恒速灌注人工脑脊液。1 h后,小鼠腹腔注射盐酸曲马多注射液50 mg.kg 1,注射完毕立即以12 min为间隔收集额叶皮质细胞外液透析液样本,连续收集6 h。用HPLC-紫外检测法测定透析液中曲马多浓度,用DAS软件拟合药时曲线,并计算药动学参数。结果显示,曲马多在小鼠额叶皮质细胞外液中的变化过程呈二室开放模型,其主要药动学参数t1/2α、t1/2β、tmax、Cmax和AUC0∞分别为(0.27±0.05)h、(2.72±0.24)h、(0.50±0.10)h、(2 110.37±291.22)μg.L 1和(4 474.51±441.79)μg.L 1.h。本实验建立了一种应用微透析采样技术研究药物在靶器官中药动学的方法,该方法操作简单、可靠;盐酸曲马多在小鼠额叶皮质细胞外液中符合二房室模型,其分布半衰期和消除半衰期分别约为0.5 h和2.7 h。
To study the pharmacokinetics of tramadol hydrochloride in the extracellular fluid of the frontal cortex of mouse brain and to explore the research methods of target organ pharmacokinetics. After the mice were anesthetized, microdialysis probes were implanted into the frontal cortex, and the artificial cerebrospinal fluid was infused to the probe at a constant rate of 2 μL · min 1. After 1 h, mice were injected intraperitoneally with tramadol hydrochloride injection 50 mg · kg -1. Immediately after the injection was completed, the samples of frontal cortex extracellular fluid dialysate were collected at 12 min intervals and collected continuously for 6 h. The concentration of tramadol in the dialysate was determined by HPLC-UV. The curve of the drug was fitted by DAS software and the pharmacokinetic parameters were calculated. The results showed that the changes of tramadol in the extracellular fluid of the frontal cortex of mice showed a two-compartment open model. The main pharmacokinetic parameters t1 / 2α, t1 / 2β, tmax, Cmax and AUC0∞ were 0.27 ± 0.05) h, (2.72 ± 0.24) h, (0.50 ± 0.10) h, (2 110.37 ± 291.22) μg.L 1, and (4747.51 ± 441.79) μg.L 1.h.Conclusion: This experiment established a method of using microdialysis sampling technology to study the pharmacokinetics of drugs in target organs. The method is simple and reliable. The tramadol hydrochloride in the mouse frontal cortex extracellular fluid meets the two-compartment model, and its distribution Half-life and elimination half-lives were about 0.5 h and 2.7 h, respectively.