Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics
Introduction 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 pharmacokineti...
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| Format: | Article |
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Taylor & Francis Group
2025-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2025.2496792 |
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| author | Janthima Methaneethorn Zheng Jiao Rowan AlEjielat Totsapol Jirasomprasert |
| author_facet | Janthima Methaneethorn Zheng Jiao Rowan AlEjielat Totsapol Jirasomprasert |
| author_sort | Janthima Methaneethorn |
| collection | DOAJ |
| description | Introduction 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.Methods 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.Results Fifteen studies were included. The volume of distribution (Vd) 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 Vd. 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.Conclusions 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.PROSPERO Registration CRD42024609484. |
| format | Article |
| id | doaj-art-20879f54dec145ec96c816a84abd42bc |
| institution | DOAJ |
| issn | 0785-3890 1365-2060 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj-art-20879f54dec145ec96c816a84abd42bc2025-08-20T03:10:11ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2496792Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokineticsJanthima Methaneethorn0Zheng Jiao1Rowan AlEjielat2Totsapol Jirasomprasert3Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandDepartment of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaFaculty of Pharmacy and Medical Sciences, University of Petra, Amman, JordanDivision of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, ThailandIntroduction 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.Methods 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.Results Fifteen studies were included. The volume of distribution (Vd) 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 Vd. 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.Conclusions 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.PROSPERO Registration CRD42024609484.https://www.tandfonline.com/doi/10.1080/07853890.2025.2496792Azithromycinpopulation pharmacokineticsnonlinear mixed effect modelMonte Carlo simulationsindividualized dose |
| spellingShingle | Janthima Methaneethorn Zheng Jiao Rowan AlEjielat Totsapol Jirasomprasert Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics Annals of Medicine Azithromycin population pharmacokinetics nonlinear mixed effect model Monte Carlo simulations individualized dose |
| title | Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics |
| title_full | Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics |
| title_fullStr | Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics |
| title_full_unstemmed | Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics |
| title_short | Influential predictors of azithromycin pharmacokinetics: a systematic review of population pharmacokinetics |
| title_sort | influential predictors of azithromycin pharmacokinetics a systematic review of population pharmacokinetics |
| topic | Azithromycin population pharmacokinetics nonlinear mixed effect model Monte Carlo simulations individualized dose |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2025.2496792 |
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