Can Population Pharmacokinetics of Antibiotics be Extrapolated? Implications of External Evaluations

Abstract

Background and objective

External evaluation is an important issue in the population pharmacokinetic analysis of antibiotics. The purpose of this review was to summarize the current approaches and status of external evaluations and discuss the implications of external evaluation results for the future individualization of dosing regimens.

Methods

We systematically searched the PubMed and EMBASE databases for external evaluation studies of population analysis and extracted the relevant information from these articles. A total of 32 studies were included in this review.

Results

Vancomycin was investigated in 17 (53.1%) articles and was the most studied drug. Other studied drugs included gentamicin, tobramycin, amikacin, amoxicillin, ceftaroline, meropenem, fluconazole, voriconazole, and rifampicin. Nine (28.1%) studies were prospective, and the sample size varied widely between studies. Thirteen (40.6%) studies evaluated the population pharmacokinetic models by systematically searching for previous studies. Seven (21.9%) studies were multicenter studies, and 27 (84.4%) adopted the sparse sampling strategy. Almost all external evaluation studies of antibiotics (93.8%) used metrics for prediction-based diagnostics, while relatively fewer studies were based on simulations (46.9%) and Bayesian forecasting (25.0%).

Conclusion

The results of external evaluations in previous studies revealed the poor extrapolation performance of existing models of prediction- and simulation-based diagnostics, whereas the posterior Bayesian method could improve predictive performance. There is an urgent need for the development of standards and guidelines for external evaluation studies.

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Correspondence to Mao-bai Liu or Zheng Jiao.

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This work was supported by the Fujian Science and Technology Innovation Joint Project (no. 2017Y9036) and Wu Jieping Medical Foundation (no. 320.6750.2020-04-47).

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Yu Cheng, Chen-yu Wang, Zi-ran Li, Yan Pan, Mao-bai Liu, and Zheng Jiao have no conflicts of interest that are directly relevant to the content of this study.

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YC carried out the literature search and wrote the first draft of the manuscript; CW, ZL, and YP developed the search strategy and reviewed the articles; ZJ conceptualized the study; ML and ZJ supervised the study and reviewed the entire contents of the manuscript. All authors have read and agree to the published version of the manuscript.

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Cheng, Y., Wang, Cy., Li, Zr. et al. Can Population Pharmacokinetics of Antibiotics be Extrapolated? Implications of External Evaluations. Clin Pharmacokinet 60, 53–68 (2021). https://doi.org/10.1007/s40262-020-00937-4

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