Bu-Fan Yao1, Yue-E Wu1, Bo-Hao Tang1, Guo-Xiang Hao1, Evelyne Jacqz-Aigrain2,3, John van den Anker4,5,6, Wei Zhao7,8. 1. 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. 2. Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France. 3. Clinical Investigation Center CIC1426, INSERM, Paris, France. 4. Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA. 5. Departments of Pediatrics, Pharmacology and Physiology, Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. 6. Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland. 7. 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. 8. NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Shandong University, Jinan, China. zhao4wei2@hotmail.com.
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.
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.
Authors: Evelyne Jacqz-Aigrain; Stéphanie Leroux; Alison H Thomson; Karel Allegaert; Edmund V Capparelli; Valérie Biran; Nicolas Simon; Bernd Meibohm; Yoke-Lin Lo; Remedios Marques; José-Esteban Peris; Irja Lutsar; Jumpei Saito; Hidefumi Nakamura; Johannes N van den Anker; Mike Sharland; Wei Zhao Journal: J Antimicrob Chemother Date: 2019-08-01 Impact factor: 5.790
Authors: Jeffrey J Cies; Wayne S Moore; Kristen Nichols; Chad A Knoderer; Dominick M Carella; Arun Chopra Journal: Pediatr Crit Care Med Date: 2017-10 Impact factor: 3.624
Authors: Lorry G Rubin; Pablo J Sánchez; Jane Siegel; Gail Levine; Lisa Saiman; William R Jarvis Journal: Pediatrics Date: 2002-10 Impact factor: 7.124