Title

Predictive Performance of Pharmacokinetic Model-Based Virtual Trials of Vancomycin in Neonates: Mathematics Matches Clinical Observation

Authors

Bu-Fan Yao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China.
Yue-E Wu, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China.
Bo-Hao Tang, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China.
Guo-Xiang Hao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China.
Evelyne Jacqz-Aigrain, Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France.
John van den Anker, Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.
Wei Zhao, Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No.44, Wenhua West Road, Jinan, 250012, Shandong Province, China. zhao4wei2@hotmail.com.

Document Type

Journal Article

Publication Date

7-1-2022

Journal

Clinical pharmacokinetics

Volume

61

Issue

7

DOI

10.1007/s40262-022-01128-z

Abstract

BACKGROUND AND OBJECTIVE: Vancomycin is frequently used to treat Gram-positive bacterial infections in neonates. However, there is still no consensus on the optimal initial dosing regimen. This study aimed to assess the performance of pharmacokinetic model-based virtual trials to predict the dose-exposure relationship of vancomycin in neonates. METHODS: The PubMed database was searched for clinical trials of vancomycin in neonates that reported the percentage of target attainment. Monte Carlo simulations were performed using nonlinear mixed-effect modeling to predict the dose-exposure relationship, and the differences in outcomes between virtual trials and real-world data in clinical studies were calculated. RESULTS: A total of 11 studies with 14 dosing groups were identified from the literature to evaluate dose-exposure relationships. For the ten dosing groups where the surrogate marker for exposure was the trough concentration, the mean ± standard deviation (SD) for the target attainment between original studies and virtual trials was 3.0 ± 7.3%. Deviations between - 10 and 10% accounted for 80% of the included dosing groups. For the other four dosing groups where the surrogate marker for exposure was concentration during continuous infusion, all deviations were between - 10 and 10%, and the mean ± SD value was 2.9 ± 4.5%. CONCLUSION: The pharmacokinetic model-based virtual trials of vancomycin exhibited good predictive performance for dose-exposure relationships in neonates. These results might be used to assist the optimization of dosing regimens in neonatal practice, avoiding the need for trial and error.

Department

Pediatrics

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