| 引用本文: | 陈建忠，侴桂新，王长虹，王峥涛.去甲异波尔定及其代谢产物的药动学与生物利用度研究[J].中国现代应用药学,2012,29(6):473-477. |
| CHEN Jianzhong, CHOU Guixin, WANG Changhong, WANG Zhengtao.Pharmacokinetics and Bioavailability of Norisoboldine and its Metabolite in Rats[J].Chin J Mod Appl Pharm(中国现代应用药学),2012,29(6):473-477. |
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| 摘要: |
| 目的 研究去甲异波尔定静脉注射和灌胃给药后，其原型药物和主要代谢物去甲异波尔定-9-O-α-葡萄糖醛酸苷在大鼠体内的药动学特征和生物利用度。方法 以SD大鼠为模型动物，采用超高效液相色谱质谱检测法测定去甲异波尔定及其葡萄糖醛酸苷的血药浓度，并计算药动学参数。结果 去甲异波尔定及其葡萄糖醛酸苷的绝对生物利用度分别为2.77%和88.6%。大鼠静脉注射给药后，去甲异波尔定及其葡萄糖醛酸苷的药动学参数t1/2分别为(42.16±36.56)和(275.26±176.89)min，AUC0-t分别为(55.25±22.97)和(584.57±216.18)mg·min·mL-1，ke分别为(0.024 9±0.012 9)和(0.003 7± 0.002 4)min-1。大鼠灌胃给药后，去甲异波尔定及其葡萄糖醛酸苷的药动学参数Cmax分别为(0.14±0.03)和(13.80± 1.46)mg·mL-1，Tmax分别为(23.33±13.29)和(45.00±9.49)min，t1/2分别为(30.20±11.04)和(313.79±181.20)min，AUC0-t分别为(9.17±2.44)和(3 108.69±299.45)mg·min·mL-1，ke分别为(0.025 2±0.007 6)和(0.002 7±0.001 0)min-1。统计学检验表明，静脉注射和灌胃给药后去甲异波尔定及其葡萄糖醛酸苷的t1/2、AUC0-t、Tmax、Cmax、ke和MRT之间均有显著性差异(P<0.05)。结论 去甲异波尔定在体内生物转化迅速且生物利用度低。与原型药物相比，去甲异波尔定葡萄糖醛酸苷在体内的血药浓度较高且消除缓慢。 |
| 关键词: 去甲异波尔定 代谢产物 药动学 生物利用度 乌药 |
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| 基金项目:国家重大新药创制专项(2009ZX09103-374)；国家自然科学基金项目(81102882)；上海市科委中药现代化专项(09dz1972100) |
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| Pharmacokinetics and Bioavailability of Norisoboldine and its Metabolite in Rats |
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CHEN Jianzhong, CHOU Guixin, WANG Changhong, WANG Zhengtao1,2,3
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1.The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;2.School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;3.Shanghai R＆D Centre for Standardization of Chinese Medicines, Shanghai 201203, China
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| Abstract: |
| OBJECTIVE To investigate the in vivo pharmacokinetic properties and bioavailability of norisoboldine and its major metabolite in rats after intravenous and oral administration. METHODS A UPLC-MS method was used to determine the plasma concentrations of norisoboldine and norisoboldine-9-O-α-glucuronide in rats plasma. The pharmacokinetic parameters were calculated with PK solution software. RESULTS The absolute bioavailabilities for norisoboldine and norisoboldine-9-O-α-glucuronide were 2.77% and 88.6%, respectively. After intravenous injection of norisoboldine, the main pharmacokinetic parameters of norisoboldine and norisoboldine-9-O-α-glucuronide were as follows: t1/2 (42.16±36.56) and (275.26±176.89) min, AUC0-t(55.25±22.97) and (584.57±216.18)mg·min·mL-1, ke (0.024 9±0.012 9) and (0.003 7±0.002 4)min-1, respectively. Their major pharmacokinetic parameters after oral administration were as follows: Cmax (0.14±0.03) and (13.80±1.46)mg·mL-1, Tmax (3.33±13.29) and (45.00±9.49)min, t1/2 (30.20±11.04) and (313.79±181.20)min, AUC0-t (9.17±2.44) and (3 108.69±299.45) mg·min·mL-1, ke (0.025 2±0.007 6) and (0.002 7±0.001 0)min-1, respectively. There were significant differences between oral and intravenous administration in t1/2, AUC0-t, Tmax, Cmax, ke and MRT (P<0.05). CONCLUSION The absolute bioavailability for norisoboldine was poor in rats. Norisoboldine could be quickly biotransformed into norisoboldine-9-O-α-glucuronide, a major metabolite of parent drug in vivo, and the plasma concentration of norisoboldine-9-O-α-glucuronide was considerably higher than that of the parent drug. |
| Key words: norisoboldine metabolite pharmacokinetics bioavailability Linderae Radix |
