Methaneethorn Janthima, Jiao Zheng, AlEjielat Rowan, Jirasomprasert Totsapol
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ann Med. 2025 Dec;57(1):2496792. doi: 10.1080/07853890.2025.2496792. Epub 2025 May 15.
Azithromycin exhibits significant pharmacokinetic variability. Thus, dosage optimization is crucial for optimal therapeutic outcomes. This systematic review aims to analyze the population pharmacokinetics (PopPK) of azithromycin and identify key covariates influencing its pharmacokinetics.
A systematic search was conducted in PubMed, Scopus, and ScienceDirect databases. Azithromycin PopPK studies conducted using a nonlinear mixed-effects approach in humans were included. Studies published in non-English or non-Thai languages were excluded. Moreover, studies with insufficient information, review articles, or registered protocols were also excluded. The reporting quality of the included studies was assessed using adapted guidelines from a previously published framework. Data on study designs, population characteristics, pharmacokinetic parameters, and influential predictors were summarized. Forest plots were used to determine the influence of covariates on azithromycin pharmacokinetics.
Fifteen studies were included. The volume of distribution () and the clearance in preterm newborns were approximately 68%-94% and 87%-100% lower than those of adults and children. Pregnant women had approximately 85% higher . Patients with alanine aminotransferase >40 U/L had about 24% lower clearance. Azithromycin clearance slightly decreased with advancing age. There is limited data on the relationship between azithromycin exposure and safety outcomes. Finally, most models were not externally evaluated.
Significant predictors for azithromycin pharmacokinetics were identified in this review. However, the limited external validation of most models restricts their clinical utility. Further research is necessary to confirm the models' external validity.
CRD42024609484.
阿奇霉素表现出显著的药代动力学变异性。因此，剂量优化对于实现最佳治疗效果至关重要。本系统评价旨在分析阿奇霉素的群体药代动力学（PopPK），并确定影响其药代动力学的关键协变量。
在PubMed、Scopus和ScienceDirect数据库中进行了系统检索。纳入了在人类中使用非线性混合效应方法进行的阿奇霉素PopPK研究。排除以非英语或非泰语发表的研究。此外，信息不足的研究、综述文章或注册方案也被排除。使用先前发表框架中的改编指南评估纳入研究的报告质量。总结了关于研究设计、人群特征、药代动力学参数和有影响的预测因素的数据。使用森林图确定协变量对阿奇霉素药代动力学的影响。
纳入了15项研究。早产儿的分布容积（）和清除率比成人和儿童分别低约68%-94%和87%-100%。孕妇的分布容积高约85%。丙氨酸氨基转移酶>40 U/L的患者清除率约低24%。阿奇霉素清除率随年龄增长略有下降。关于阿奇霉素暴露与安全性结果之间关系的数据有限。最后，大多数模型未进行外部评估。
本综述确定了阿奇霉素药代动力学的重要预测因素。然而，大多数模型有限的外部验证限制了它们的临床应用。需要进一步研究以确认模型的外部有效性。
PROSPERO注册：CRD42024609484。
