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左旋奥硝唑及磷酸左奥硝唑酯二钠在大鼠体内药代动力学比较研究

肖亚楠, 孙建国, 万萍, 王广基

肖亚楠, 孙建国, 万萍, 王广基. 左旋奥硝唑及磷酸左奥硝唑酯二钠在大鼠体内药代动力学比较研究[J]. 中国药科大学学报, 2014, 45(5): 571-575. DOI: 10.11665/j.issn.1000-5048.20140512
引用本文: 肖亚楠, 孙建国, 万萍, 王广基. 左旋奥硝唑及磷酸左奥硝唑酯二钠在大鼠体内药代动力学比较研究[J]. 中国药科大学学报, 2014, 45(5): 571-575. DOI: 10.11665/j.issn.1000-5048.20140512
XIAO Yanan, SUN Jianguo, WAN Ping, WANG Guangji. Pharmacokinetics of(S)-ornidazole and(S)-ornidazole phosphate disodium in rats[J]. Journal of China Pharmaceutical University, 2014, 45(5): 571-575. DOI: 10.11665/j.issn.1000-5048.20140512
Citation: XIAO Yanan, SUN Jianguo, WAN Ping, WANG Guangji. Pharmacokinetics of(S)-ornidazole and(S)-ornidazole phosphate disodium in rats[J]. Journal of China Pharmaceutical University, 2014, 45(5): 571-575. DOI: 10.11665/j.issn.1000-5048.20140512

左旋奥硝唑及磷酸左奥硝唑酯二钠在大鼠体内药代动力学比较研究

基金项目: 江苏省药代动力学重点实验室提升项目(No.BM2012012)

Pharmacokinetics of(S)-ornidazole and(S)-ornidazole phosphate disodium in rats

  • 摘要: 采用手性色谱LC-MS/MS法同时检测左旋和右旋奥硝唑,比较研究左旋奥硝唑[(S)-ONZ]及磷酸左奥硝唑酯二钠[(S)-ONZ-P]在大鼠体内的药代动力学差异,并监测是否发生手性转化。结果表明,大鼠单次iv给予25,50,100 mg/kg(S)-ONZ及等物质的量(S)-ONZ-P后,(S)-ONZ-P在SD大鼠体内迅速转化为(S)-ONZ,平均转化时间介于1.57~3.86 min。两组大鼠血浆中(S)-ONZ的t1/2分别为2.04~2.31 h;2.02~2.51 h;AUC0-∞与剂量间呈良好的线性关系,呈线性动力学过程。(S)-ONZ,(S)-ONZ-P在大鼠体内药代动力学行为无显著差异,且二者均不转化生成(R)-ONZ。
    Abstract: The aims of this study were to conduct the comparative evaluation of pharmacokinetic of(S)-ornidazole [(S)-ONZ] and(S)-ornidazole phosphate disodium [(S)ONZ-P] in rats, and to observe the potential chiral transformation to(R)-ornidazole [(R)-ONZ] using developed LC-MS/MS method. After single, intravenous administration of 25, 50, 100 mg/kg(S)-ONZ and(S)-ONZ-P [equal molarity to that of(S)-ONZ], it was found that there existed linearity between the calculated areas under the curve(AUC0-∞)and dose. And elimination half-time(t1/2 )of(S)-ONZ was calculated to be 2. 04-2. 31 h and 2. 02-2. 51 h, respectively. After iv dosing of(S)-ONZ-P, (S)-ONZ-P quickly transferred into(S)-ONZ with the average transformation time of around 1. 57 to 3. 86 min. No significant differences in pharmacokinetics between the two drugs were found in rats. There was no(R)-ONZ detected in the plasma using both(S)-ONZ and(S)-ONZ-P.
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  • 刊出日期:  2014-10-24

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