COMPARISON OF ACTIVITIES OF RIFAPENTINE AND RIFAMPIN AGAINST MYCOBACTERIUM-TUBERCULOSIS RESIDING IN HUMAN MACROPHAGES
COMPARISON OF ACTIVITIES OF RIFAPENTINE AND RIFAMPIN AGAINST MYCOBACTERIUM-TUBERCULOSIS RESIDING IN HUMAN MACROPHAGES
复制标题
DOI：
10.1128/aac.39.9.2073
复制
发表时间：
1995-09-01
影响因子：
4.9
通讯作者：
HEIFETS, L
中科院分区：
文献类型：
--
作者：
MOR, N;SIMON, B;HEIFETS, L
测定了利福喷丁和利福平对人单核细胞源性巨噬细胞结核分枝杆菌的活性。利福喷丁对胞内细菌的mic和MBCs比利福平低2 - 4倍，对胞外细菌的mic和MBCs差异不明显。然而，利福喷丁比利福平更有利的药代动力学在其他实验模型中得到了解决。这些模型显示，感染的巨噬细胞在短脉冲暴露于药物后，以及当感染的巨噬细胞暴露于变化的药物浓度（模仿血液中观察到的药代动力学曲线）时，存在实质性差异。每周一次暴露于利福喷丁浓度，相当于血液中600毫克剂量后获得的浓度，结果在第一周内细菌数量急剧下降。这种下降在四周内保持在最低水平。这项研究的结果表明利福喷丁适合间歇性治疗方案。在这项研究中发现，利福喷丁的长期作用可能与细胞内积聚的高比率有关，这是利福平的四到五倍。进一步研究利福霉素在细胞内的分布以及药物与巨噬细胞内细菌的实际相互作用位点是必要的。
The activities of rifapentine and rifampin against Mycobacterium tuberculosis residing in human monocyte-derived macrophages were determined. The MICs and MBCs of rifapentine for intracellular bacteria were two- to fourfold lower than those of rifampin, For extracellular bacteria, this difference was less noticeable. Nevertheless, the more favorable pharmacokinetics of rifapentine over rifampin was addressed in other experimental models. These models showed substantial differences after short pulsed exposures of the infected macrophages to the drugs and when the infected macrophages were exposed to changing drug concentrations that imitated the pharmacokinetic curves observed in blood, Once-a-week exposures to rifapentine concentrations equivalent to those attained in blood after one 600-mg dose resulted during the first week in a dramatic decline in the number of bacteria, and this decline was maintained at a minimal level for a period of four weeks. The results of this study have shown the suitability of rifapentine for intermittent-treatment regimens. The prolonged effect of rifapentine found in this study may be associated with high ratios of intracellular accumulation, which were four- to fivefold higher than those found for rifampin. Further studies on the intracellular distribution of rifamycins and on the sites of actual interaction between the drugs and bacteria residing in macrophages are necessary.