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在实验性鼠结核病中,通过脾脏的活菌计数对长效利福霉素,利福喷丁(RPE)和FCE22807(FCE)的有效性进行了研究。用结核分支杆菌H37R_v株感染两周后,采用异烟肼25mg/kg、利福平10mg/kg和吡嗪酰胺150mg/kg,每日给药进行治疗持续6周。此后将小鼠分组,给RPE或FCE间隔分别为1周、2周或3周,化疗18周和24周后进行脾脏活菌计数。实验1显示RPE的剂量很有效,在每周给药1次的方案中,16mg/kg的剂量迅速灭菌,10mg/kg灭菌作用不十分迅速,6.25mg/kg作用不完全。RPE每2周或3周给药作用小,每2周给药16mg/kg其作用尽管与6mg/kg每周给药相同。第二个实验比较了RPE和FCE每次给药12mg/kg或8mg/kg。8mg/kg每2周或3周给药结果相似,尽管FCE较RPE作用稍强。血清分析表明8mg/kg及12mg/kgFCE的血清水平甚至低于6.25mg/kgRPE所产生的水平。这提示如果FCE的生物利用度可以提高,该药可能是较RPE更好的药物,并且服用16mg/kgRPE后的血清水平与人服用8mg/kg同时摄入富有脂肪的食物后的水平相似,提示在人类治疗中有效的2周给药1次的良好前景,对长效利福霉素在肺结核治疗管理中可能发挥的作用进行了讨论。
In experimental murine tuberculosis, the efficacy of long-acting rifamycin, rifapentine (RPE) and FCE22807 (FCE) was investigated by viable counts of the spleen. Two weeks after infection with Mycobacterium tuberculosis H37R_v strain, isoniazid 25 mg / kg, rifampin 10 mg / kg and pyrazinamide 150 mg / kg were administered daily for 6 weeks. Mice were then pooled and spleen viable count was performed for RPE or FCE intervals of 1 week, 2 weeks, or 3 weeks, respectively, after 18 weeks and 24 weeks of chemotherapy. Experiment 1 shows that the dose of RPE is very effective. In the regimen of once-weekly administration, the dose of 16 mg / kg is rapidly sterilized, the sterilization effect of 10 mg / kg is not very rapid, and the effect of 6.25 mg / kg is not complete. RPE is administered less every 2 weeks or 3 weeks and 16 mg / kg every 2 weeks although it is the same as 6 mg / kg weekly dosing. The second experiment compared RPE and FCE to 12 mg / kg or 8 mg / kg each time. The results of the dosing at 8 mg / kg every 2 weeks or 3 weeks were similar, although the effect of FCE was slightly stronger than that of RPE. Serum analysis showed serum levels of 8 and 12 mg / kg of FCE were even lower than the levels produced by 6.25 mg / kg RPE. This suggests that if the bioavailability of FCE is increased, the drug may be a better drug than RPE and the serum level following 16 mg / kg RBE is similar to that of humans taking 8 mg / kg of fat-rich food, suggesting A good prospect of effective once-weekly administration of human once-twice-weekly administration of rifamycin in tuberculosis treatment management is discussed.