Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-spe...Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.展开更多
Sensitive and selective liquid chromatography-tandem mass spectrometry methods have been developed and validated for the determination of delamanid in mouse plasma and lung. Sample preparation involved liquid-liquid e...Sensitive and selective liquid chromatography-tandem mass spectrometry methods have been developed and validated for the determination of delamanid in mouse plasma and lung. Sample preparation involved liquid-liquid extraction with diethyl ether for plasma, or protein precipitation followed by liquid-liquid extraction with tert-butyl methyl ether for lung homogenate. Chromatographic separation was performed on a reversed phase column with a linear gradient elution using purified water-formic acid (1000:2, v/v) and methanol-formic acid (1000:2, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive ion electrospray ionization in the selected reaction monitoring mode. The analytical methods were successfully validated for selectivity, calibration curve, accuracy, precision, extraction recovery, and stability over a range of 6 - 1000 ng/mL for plasma and 10 - 1000 ng/mL for lung homogenate. The validated methods were successfully applied for evaluation of pharmacokinetics of delamanid in male mice.展开更多
目的:探索抗耐多药结核病(multidrug resistant tuberculosis, MDR-TB)药物贝达喹啉及德拉马尼不良反应(adverse drug reaction, ADR),从多角度分析两药ADR上报的相关情况,为临床治疗制定相应药学监护策略,为新的研究思路和方向提供线...目的:探索抗耐多药结核病(multidrug resistant tuberculosis, MDR-TB)药物贝达喹啉及德拉马尼不良反应(adverse drug reaction, ADR),从多角度分析两药ADR上报的相关情况,为临床治疗制定相应药学监护策略,为新的研究思路和方向提供线索。方法:利用美国食品药品监督管理局(Food and Drug Administration, FDA)公共数据开放项目openFDA (U.S. Food and Drug Administration Public Data Open Project, openFDA)数据库中的药品不良反应的交互式图表板块访问不良反应的应用程序端口(application programming interface, API),检索2004年1月1日至2021年2月5日期间,贝达喹啉和德拉马尼的ADR上报情况,并进行多角度分析。结果:贝达喹啉和德拉马尼的ADR上报数分别为1 547份和1 220份,ADR主要由医师上报,上报国家主要为南非,年龄主要集中在20~40岁之间,性别上无显著性差异,用药适应证主要为肺部结核感染,主要的ADR为QT间期延长和呕吐。结论:在使用贝达喹啉和德拉马尼期间关注QT间期,注意胃肠道反应、贫血、呼吸困难和周围神经系统损伤等不良反应。利用openFDA数据库能对贝达喹啉和德拉马尼的ADR相关信息进行全面、多角度的分析和阶段性的总结。此外,需加强我国的不良反应上报积极性。展开更多
基金supported by the Beijing Municipal Science&Technology Commission(Z191100006619077).
文摘Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.
文摘Sensitive and selective liquid chromatography-tandem mass spectrometry methods have been developed and validated for the determination of delamanid in mouse plasma and lung. Sample preparation involved liquid-liquid extraction with diethyl ether for plasma, or protein precipitation followed by liquid-liquid extraction with tert-butyl methyl ether for lung homogenate. Chromatographic separation was performed on a reversed phase column with a linear gradient elution using purified water-formic acid (1000:2, v/v) and methanol-formic acid (1000:2, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive ion electrospray ionization in the selected reaction monitoring mode. The analytical methods were successfully validated for selectivity, calibration curve, accuracy, precision, extraction recovery, and stability over a range of 6 - 1000 ng/mL for plasma and 10 - 1000 ng/mL for lung homogenate. The validated methods were successfully applied for evaluation of pharmacokinetics of delamanid in male mice.
文摘目的:探索抗耐多药结核病(multidrug resistant tuberculosis, MDR-TB)药物贝达喹啉及德拉马尼不良反应(adverse drug reaction, ADR),从多角度分析两药ADR上报的相关情况,为临床治疗制定相应药学监护策略,为新的研究思路和方向提供线索。方法:利用美国食品药品监督管理局(Food and Drug Administration, FDA)公共数据开放项目openFDA (U.S. Food and Drug Administration Public Data Open Project, openFDA)数据库中的药品不良反应的交互式图表板块访问不良反应的应用程序端口(application programming interface, API),检索2004年1月1日至2021年2月5日期间,贝达喹啉和德拉马尼的ADR上报情况,并进行多角度分析。结果:贝达喹啉和德拉马尼的ADR上报数分别为1 547份和1 220份,ADR主要由医师上报,上报国家主要为南非,年龄主要集中在20~40岁之间,性别上无显著性差异,用药适应证主要为肺部结核感染,主要的ADR为QT间期延长和呕吐。结论:在使用贝达喹啉和德拉马尼期间关注QT间期,注意胃肠道反应、贫血、呼吸困难和周围神经系统损伤等不良反应。利用openFDA数据库能对贝达喹啉和德拉马尼的ADR相关信息进行全面、多角度的分析和阶段性的总结。此外,需加强我国的不良反应上报积极性。
