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• W4316013558 abstract "Physiologically based pharmacokinetic (PBPK) models consist of compartments representing different tissues. As most models are only verified based on plasma concentrations, it is unclear how reliable associated tissue profiles are. This study aimed to assess the accuracy of PBPK-predicted beta-lactam antibiotic concentrations in different tissues and assess the impact of using effect site concentrations for evaluation of target attainment. Adipose, bone, and muscle concentrations of five beta-lactams (piperacillin, cefazolin, cefuroxime, ceftazidime, and meropenem) in healthy adults were collected from literature and compared with PBPK predictions. Model performance was evaluated with average fold errors (AFEs) and absolute AFEs (AAFEs) between predicted and observed concentrations. In total, 26 studies were included, 14 of which reported total tissue concentrations and 12 unbound interstitial fluid (uISF) concentrations. Concurrent plasma concentrations, used as baseline verification of the models, were fairly accurate (AFE: 1.14, AAFE: 1.50). Predicted total tissue concentrations were less accurate (AFE: 0.68, AAFE: 1.89). A slight trend for underprediction was observed but none of the studies had AFE or AAFE values outside threefold. Similarly, predictions of microdialysis-derived uISF concentrations were less accurate than plasma concentration predictions (AFE: 1.52, AAFE: 2.32). uISF concentrations tended to be overpredicted and two studies had AFEs and AAFEs outside threefold. Pharmacodynamic simulations in our case showed only a limited impact of using uISF concentrations instead of unbound plasma concentrations on target attainment rates. The results of this study illustrate the limitations of current PBPK models to predict tissue concentrations and the associated need for more accurate models. <h3>SIGNIFICANCE STATEMENT</h3> Clinical inaccessibility of local effect site concentrations precipitates a need for predictive methods for the estimation of tissue concentrations. This is the first study in which the accuracy of PBPK-predicted tissue concentrations of beta-lactam antibiotics in humans were assessed. Predicted tissue concentrations were found to be less accurate than concurrent predicted plasma concentrations. When using PBPK models to predict tissue concentrations, this potential relative loss of accuracy should be acknowledged when clinical tissue concentrations are unavailable to verify predictions." @default.
• W4316013558 created "2023-01-14" @default.
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• W4316013558 date "2023-01-13" @default.
• W4316013558 modified "2023-09-24" @default.
• W4316013558 title "Predictive Performance of Physiologically Based Pharmacokinetic Modelling of Beta-Lactam Antibiotic Concentrations in Adipose, Bone, and Muscle Tissues" @default.
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• W4316013558 cites W1963980205 @default.
• W4316013558 cites W1969477911 @default.
• W4316013558 cites W1983118095 @default.
• W4316013558 cites W1984514551 @default.
• W4316013558 cites W1987255433 @default.
• W4316013558 cites W2007355475 @default.
• W4316013558 cites W2009316291 @default.
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• W4316013558 cites W2025412733 @default.
• W4316013558 cites W2026015795 @default.
• W4316013558 cites W2027143209 @default.
• W4316013558 cites W2028165836 @default.
• W4316013558 cites W2034200280 @default.
• W4316013558 cites W2035298668 @default.
• W4316013558 cites W2039250788 @default.
• W4316013558 cites W2040762948 @default.
• W4316013558 cites W2048297771 @default.
• W4316013558 cites W2058983341 @default.
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• W4316013558 cites W2140412742 @default.
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• W4316013558 cites W2168749478 @default.
• W4316013558 cites W2325635634 @default.
• W4316013558 cites W2327876581 @default.
• W4316013558 cites W2329671310 @default.
• W4316013558 cites W2509227394 @default.
• W4316013558 cites W2743330961 @default.
• W4316013558 cites W2776516440 @default.
• W4316013558 cites W2795915717 @default.
• W4316013558 cites W2885748302 @default.
• W4316013558 cites W2960934439 @default.
• W4316013558 cites W2964585317 @default.
• W4316013558 cites W2972908074 @default.
• W4316013558 cites W2994982026 @default.
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• W4316013558 cites W3123685372 @default.
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• W4316013558 doi "https://doi.org/10.1124/dmd.122.001129" @default.
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• W4316013558 hasPublicationYear "2023" @default.
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