替硝唑与甲硝唑对厌氧菌的作用及其药动学比较

目的:研究替硝唑注射液在小鼠体内抗厌氧菌作用,并考察其药动学过程. 方法:用琼脂稀释法测定替硝唑在体外对三株厌氧菌的最低抑菌浓度,在厌氧消化链球菌感染小鼠模型上试验替硝唑的保护作用;采用高效液相色谱法测定替硝唑在小鼠体内浓度,3P87软件计算药动学参数. 结果:替硝唑在体外对三株厌氧菌最低抑菌浓度为0.125～1 mg/L,替硝唑和甲硝唑对厌氧消化链球菌腹腔感染小鼠ED50分别为9.6和13.2 mg/kg,替硝唑和甲硝唑的消除半衰期分别为1.86和1.26 h. 结论:替硝唑比甲硝唑在体内消除更慢,维持有效血药浓度时间更长,替硝唑体内抗厌氧菌作用更强.

Comparison of antibacterial activity and pharmacokinetics of tinidazole with metronidazole in mice

AIM: The activities and pharmacokinetics of tinidazole and metronidazole were compared in vitro and in vivo . METHODS: The susceptibility of two clinical isolates and one reference strain to tinidazole and metronidazole was determined in vitro by the agar dilution method. The efficacy of tinidazole was studied in neutropenic mice infected by Peptostreptococcus anaerobius. The plasma samples collected were analyzed by reversed phase high performance liquid chromatography on a C18 bonded silica column with UV detector at wavelength 317 nm. The parameters of pharmacokinetics were calculated with 3P87 program by computer. RESULTS: The results showed that tinidazole acted against anaerobic bacteria at a concentration of 0.125-1 mg/L. The 50% effective doses (ED50) of tinidazole and metrodazole were 9.6 and 13.2 mg/kg in the neutropenic mice infected by Peptostreptococcus anaerobius, respectively. The efficacy of tinidazole was more effective tha that of metronidazole. The elimination half lives of tinidazole and metrodazole were 1.86 and 1.26 h in mice, respectively. CONCLUSION: The elimination of tinidazole is lower and the concentrations in plasma are higher compared with those of metronidazole, suggesting that tinidazole may be more effective in the therapy of anaerobic bacterial infections.