TY -的T1 -优化吡嗪酰胺治疗肺结核的JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02013 -2020欧元六世- 58 - 1 SP - 2002013 AU -张,南AU -萨维奇,Radojka m . AU - Boeree马丁J . AU - Peloquin查尔斯·a . AU -维纳Marc盟——海因里希,Norbert盟——Bliven-SizemoreErin AU - Phillips, Patrick P.J. AU - Hoelscher, Michael AU - Whitworth, William AU - Morlock, Glenn AU - Posey, James AU - Stout, Jason E. AU - Mac Kenzie, William AU - Aarnoutse, Robert AU - Dooley, Kelly E. A2 -，Y1 - 2021/07/01 UR - //www.qdcxjkg.com/content/58/1/2002013.abstract N2 -吡嗪酰胺是一种有效的杀菌剂，可以缩短治愈结核病所需的治疗时间。它与新的和现有的结核病药物具有协同作用。吡嗪酰胺的剂量能否在保证安全性的同时优化疗效尚不确定，其在进一步缩短治疗时间方面的潜在作用也不确定。药代动力学数据、痰培养和安全实验室结果由结核病试验联盟(TBTC)研究27和28以及泛非抗结核抗生素评估联盟(PanACEA)多支多阶段结核病(mms - tb)汇编而成。在多中心2期试验中，参与者接受利福平(范围10-35 mg·kg−1)、吡嗪酰胺(范围20-30 mg·kg−1)和两种伴生药物。进行吡嗪酰胺药代动力学-药效学(PK-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)。参数生存分析显示，这种关系在地理上是不同的，非非洲参与者的PK-PD关系比非洲参与者更陡峭。 In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide Cmax increased and varied by rifampicin area under the curve (p-value<0.01). Modelling and simulation suggested that very high doses of pyrazinamide (>4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. 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'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 ER -