回顾性分析不同用药方案下吡嗪酰胺血药峰浓度与不良反应发生的差异

目的：分析吡嗪酰胺日总剂量相同，不同用药方案下血药峰浓度和不良反应发生的差异，为临床合理使用吡嗪酰胺提供客观依据。方法：收集2018年5月 ~ 2022年5月进行吡嗪酰胺血药峰浓度检测的结核患者1377例，根据吡嗪酰胺用药方案分为0.5 g tid组和1.5 g qd组，分析不同用药方案的患者血药峰浓度（Cmax）结果以及药品不良反应发生率的差异。结果：0.5 g tid组Cmax低于1.5 g qd组（P < 0.001）；0.5 g tid组中，男性与女性患者Cmax的差异无统计学意义（P = 0.832）；1.5 g qd组中，男性Cmax低于女性（P = 0.033）。0.5 g tid组Cmax在参考范围内的比例低于1.5 g qd组（P < 0.001）。研究期间共收到怀疑使用吡嗪酰胺所致药品不良反应的患者共143例，与用药方案为0.5 g tid组相比，用药方案为1.5 g qd组不良反应发生例数相对较少。结论：日总剂量相同时，吡嗪酰胺每日一次给药的Cmax明显高于每日三次给药，且不良反应发生率没有升高，建议吡嗪酰胺每日剂量一次给药。

Analysis of Plasma Peak Concentrations of Pyrazinamide and Occurrence of Adverse Reactions under Different Medication Regimens

Objective: To investigate the differences of serum peak concentrations of pyrazinamide (PZA) and incidences of adverse drug reaction (ADR) under different medication regimens with the same daily total dose, to provide objective basis for rational PZA treatments. Methods: A total of 1377 tuberculosis patients who met the criteria and underwent PZA peak concentration detection were collected from May 2018 to May 2022. According to the medication of PZA, the patients were divided into 0.5 g tid group and 1.5 g qd group. The differences in serum peak concentrations (Cmax) of patients with different medication regimens were analyzed. At the same time, ADRs after using pyrazinamide were collected, and the differences in the occurrence of ADRs under different medication regimens of pyrazinamide were compared. Results: The Cmax of patients in the 0.5 g tid group were lower than those in the 1.5 g qd group (P < 0.001). In the 1.5 g qd group, Cmax in male was lower than that in female (P = 0.033). The proportion of Cmax within the reference range in the 0.5 g tid group was lower than that in the 1.5 g qd group (P < 0.001). During the study period, a total of 143 patients appeared ADRs suspected of PZA. Compared with the 0.5 g tid group, the incidence of ADRs was lower in the 1.5 g qd group. Conclusion: With the same total daily dose, the Cmax of PZA given once daily was significantly higher than that given three times a day, and the incidence of ADRs was relatively less. Therefore, once-daily dose of pyrazinamide is recommended