| 摘要: |
| 目的：应用蒙特卡罗模拟优化注射用拉氧头孢钠在新生儿细菌感染性疾病中的初始给药方案，为临床合理用药提供参考。方法：参考2017年制定的临床和实验室标准协会标准，明确注射用拉氧头孢钠对敏感菌最低抑菌浓度（MIC）的敏感折点，结合拉氧头孢钠的药品说明书，制定15种不同MIC的初始给药方案，应用群体药物代谢动力学/药物效应动力学模型和蒙特卡洛模拟10 000例“真实患者”的获得目标概率（PTA），优化获得最佳的初始给药方案。结果：注射用拉氧头孢钠对敏感菌的敏感折点为MIC≤8 μg/mL。当MIC=1 μg/mL，所有给药方案PTA>90.0%。当MIC=2 μg/mL，除“40 mg/（kg·d）分2次给药，50 mg/（kg·d）分2次给药”方案外，其余给药方案PTA>90.0%。当MIC=4 μg/mL，“每天4次所有剂量、80 mg/（kg·d）分3次给药、70 mg/（kg·d）分3次给药、60 mg/（kg·d）分3次给药”共8种给药方案PTA>90.0%。当MIC=8 μg/mL，仅“80 mg/（kg·d）分4次给药、70 mg/（kg·d）分4次给药”两种给药方案PTA>90.0%。当4 μg/mL≤MIC≤8 μg/mL，同一给药剂量下，不同给药频次PTA比较差异有统计学意义；当MIC≤2 μg/mL，同一给药剂量下，不同给药频次PTA比较差异无统计学意义。结论：应用蒙特卡洛模拟推荐“60 mg/（kg·d）分2次给药”为注射用拉氧头孢钠在新生儿细菌感染性疾病中的初始给药方案。 |
| 关键词: 注射用拉氧头孢钠 新生儿 细菌感染性疾病 蒙特卡洛模拟 |
| DOI：doi:10.13407/ j.cnki. jpp.1672-108X.2022.06.008 |
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| 基金项目:首都医科大学附属北京妇产医院2017年中青年学科骨干培养专项课题,编号FYCC201715。 |
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| Optimization of Initial Administration Regimens for Latamoxef Sodium for Injection in Neonatal Bacterial Infectious Diseases by Monte Carlo Simulation |
| Kou Chen, Han Dong, Zhang Yanan, Gao Zhengping |
| (Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China) |
| Abstract: |
| Objective: To optimize the initial administration regimens for latamoxef sodium for injection in neonatal bacterial infectious diseases by Monte Carlo simulation, so as to provide reference for rational drug use in clinic. Methods: The sensitive breakpoint of minimal inhibitory concentration (MIC) of latamoxef sodium for injection was determined by referring to the criteria of Clinical and Laboratory Standards Association formulated in 2017. Combined with the drug instructions, 15 kinds of initial administration regimens were developed under different MIC. Through the application of population pharmacokinetic/pharmacodynamic model and Monte Carlo simulation of probability of target attainment (PTA) in 10,000 cases of “real patients”, the optimal initial administration regimen was optimized. Results: The sensitive breakpoint of latamoxef sodium for injection to the sensitive bacteria was MIC less than or equal to 8 μg/mL. When MIC was 1 μg/mL, PTA of all the administration regimens was more than 90%. When MIC was 2 μg/mL, PTA of the other administration regimens was more than 90% except for “40 mg/(kg·d) in two doses, 50 mg/(kg·d) in two doses”. When MIC was 4 μg/mL, PTA of the 8 kinds of administration regimens was more than 90% except for “all doses for 4 times a day, 80 mg/ (kg·d) in three doses, 70 mg/ (kg·d) in three doses, 60 mg/ (kg·d) in three doses”. When MIC was 8 μg/mL, PTA of the 2 kinds of administration regimens was more than 90% with “80 mg/(kg·d) in 4 doses, 70 mg/(kg·d) in four doses”. When MIC was more than or equal to 4 μg/mL and less than or equal to 8 μg/mL, PTA showed significant difference under the same dose and different administration regimens. When MIC was less than or equal to 2 μg/mL, there was no significant difference in PTA under the same dose and different administration regimens. Conclusion: Monte Carlo simulation is used to recommend “60 mg/(kg·d) in two doses” as the initial administration regimen of latamoxef sodium for injection in neonatal bacterial infectious diseases. |
| Key words: latamoxef sodium for injection neonates bacterial infectious diseases Monte Carlo simulation |
