@文章{Zhang2002013，作者= {Zhang, Nan and Savic, Radojka M. and Boeree, Martin J. and Peloquin, Charles A. and Weiner, Marc and Heinrich, Norbert and blivenen - sizemore, Erin and Phillips, Patrick P.J. and Hoelscher, Michael and Whitworth, William and Morlock, Glenn and Posey, James and Stout, Jason E. and Mac Kenzie, William and Aarnoutse, Robert and Dooley, Kelly E.}，编辑={，}，标题={优化吡嗪amide治疗结核病}，volume = {58}， number = {1}，位置-id ={2002013}，年份= {2021}，doi ={10.1183/13993003.02013-2020}，出版商={欧洲呼吸学会}，摘要={吡嗪酰胺是一种有效的消188bet官网地址毒剂，可缩短治疗结核病所需的治疗时间。它与新的和现有的结核病药物协同作用。吡嗪酰胺在保持安全的同时优化疗效的剂量是不确定的，因为它在进一步缩短治疗时间方面的潜在作用也是不确定的。药代动力学数据、痰培养和安全实验室结果来自结核病试验联盟(TBTC)研究27和28以及泛非抗结核抗生素评估联盟(PanACEA)多臂多阶段结核病(mans - tb)，多中心2期试验，参与者接受利福平(范围10 35 mg{textperiodcentered}kg-1)，吡嗪酰胺(范围20 30 mg{textperiodcentered}kg-1)和两种伴药。进行吡嗪酰胺药代动力学药效学(PK{\textendash}PD)和药代动力学毒性分析。在TBTC研究中(n=77)，较高的吡嗪酰胺最大浓度(Cmax)与较短的培养转化时间(TTCC)和较高的2个月培养转化概率相关(p值\<0.001)。参数生存分析表明，这种关系在地理上有所不同，非非洲参与者的PK与PD关系比非洲参与者更陡峭。在PanACEA mam - tb (n=363)中，TTCC随吡嗪酰胺Cmax的增加而降低，并随曲线下利福平面积的变化而变化(p-value\<0.01)。建模和模拟表明，需要非常高剂量的吡嗪酰胺(\>4500 mg)或同时增加吡嗪酰胺和利福平，才能达到缩短治疗时间的目标。 Combining all trials, liver toxicity was rare (3.9\% with grade 3 or higher liver function tests (LFT)), and no relationship was seen between pyrazinamide Cmax and LFT levels.Pyrazinamide{\textquoteright}s microbiological efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel.The activity of pyrazinamide, a critical drug for tuberculosis treatment, increases as drug concentrations go up, but optimising this drug alone is unlikely to result in treatment shortening. Rather, rifampicin dosing must increase in parallel. https://bit.ly/2KenbHW}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/58/1/2002013}, eprint = {//www.qdcxjkg.com/content/58/1/2002013.full.pdf}, journal = {European Respiratory Journal} }