dFG-53 的基础药代动力学特征及其 PK/PD 相关性分析

	dFG-53 的基础药代动力学特征及其 PK/PD 相关性分析; Basic pharmacokinetic characteristics of dFG-53 and its PK/PD correlation analysis
	刘爽
导师	赵金华
摘要	The main research contents and results of this paper are as follow: 1. The establishment of analysis method of dFG-53 in plasma and urine. (1) A biological method for quAntitative analysis of dFG-53 concentration in plasma was established, using the Anti-iXase activity detected methodology : At plasma concentration ranged from 0.0625 to 16.0 μg/mL, dFG-53 concentrations were linearily correlated with the anti-iXase activity (R2 > 0.99). The intra-day and inter-day precision of quality control samples are less than 15%, and the accuracy is within 80% ~ 120%. The stability of plasma samples showed that dFG-53 was relatively stable at -20℃ for one month. The anti-iXase activity analysis method for determining dFG-53 concentration in plasma showed that the linear correlation, precision, accuracy, linear dilution and stability of the plasma dFG-53 met the requirements of quantitative analysis of biological samples. Therefore, this method can be used for the determination of dFG-53 concentration in rat plasma. (2) A biological method for quantitative analysis of dFG-53 concentration in urine was established, using activated partial thromboplastin times (APTT)detected methodology. 2. Preliminary pharmacokinetics of dFG-53 in rats. (1) After dFG-53 i.v. or s.c. injection, the pharmacokinetic parameters were calculated by DAS software, which was consistent with the two-compartment model. (2) Cmax and AUC0-∞ of dFG-53 after iv or sv to rats at different doses were positively correlated with dose, indicating that dFG-53 presented linear pharmacokinetic characteristics in rats. (3) The absolute bioavailabilities of dFG-53 after administration to rats at the three dosage (i.e., 5.00, 9.00 and 16.2 mg/kg) were 88.9%、 89.2%、 122%. (4) The urine concentration of dFG-53 after single intravenous (5.20 mg/kg) and subcutaneous (5.00 mg/kg) administration was detected by APTT activity assays, and the results showed that the cumulative excretion rates at 0 ~ 48 h were 53.7% and 60.1% , respectively. (5) The structure of dFG-53 metabolites was preliminarily by spectral methos usch as UV, 1H NRM. And the results showed that dFG-53 was excreted from the kidney in its prototype form. 3. Correlation analysis of PD/PK of dFG-53 administration to rats. The pharmacodynamic characteristics of dFG-53 after administration to rats were analyzed by APTT assays. The results showed that dFG-53 by s.c. injection and i.v. injection both sifnificantly prolonged in rat plasma APTT. PD/PK correlation analysis shows that the dFG-53 i.v. and s.c. , after the different time points of dFG-53 administration, the APTT and the plasma drug concentration showed good linear correlation, which was consistent with the results of in vitro APTT assays.
	2019-11
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74157
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	刘爽. dFG-53 的基础药代动力学特征及其 PK/PD 相关性分析, Basic pharmacokinetic characteristics of dFG-53 and its PK/PD correlation analysis[D],2019.

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