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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)g.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)g.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)g.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。
Objective To study the pharmacokinetics of norvalipol-9-O-α-glucuronide in rats after intravenous and gavage administration of norvalobal and its main metabolite And bioavailability. Methods SD rats were used as model animals. The plasma concentrations of noroporibine and glucuronide were determined by ultra performance liquid chromatography-mass spectrometry. The pharmacokinetic parameters were calculated. Results The absolute bioavailability of norpolbudine and its glucuronide were 2.77% and 88.6%, respectively. The pharmacokinetic parameters t1 / 2 of norvoproglitine and its glucuronide were (42.16 ± 36.56) and (275.26 ± 176.89) min, respectively, and the AUC0-t were (55.25 ± 22.97) and (584.57 ± 216.18) g.min.mL 1 and ke were (0.024 9 ± 0.012 9) and (0.003 7 ± 0.002 4) min 1, respectively. After intragastric administration, the pharmacokinetic parameters Cmax of desferrizol and glucuronide were (0.14 ± 0.03) and (13.80 ± 1.46) g.mL 1, respectively, and Tmax were (23.33 ± The mean AUC0 t was (9.17 ± 2.44) and (3 108.69 ± 299.45) g.min.mL 1, respectively (13.29) and (45.00 ± 9.49) min, t1 / 2 were (30.20 ± 11.04) and (313.79 ± 181.20) , ke (0.025 2 ± 0.007 6) and (0.002 7 ± 0.001 0) min 1, respectively. Statistical tests showed that the values of t1 / 2, AUC0 t, Tmax, Cmax, ke and MRT were significantly different between norvopamil and glucuronide after intravenous and intragastric administration ). Conclusion Norifolding is rapidly biologically converted and has low bioavailability in vivo. Compared with the prototype drugs, descending isoproterenol glucuronide plasma concentration in the body and the elimination of slow.