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已发表论文
替考拉宁在儿科人群中的群体药代动力学模型的综合分析：年龄相关变异性及剂量优化的意义
Authors Yu B , Wan Y, Ji W, Mao J , Zhang R, Shen Z, Hu Y, Cai H
Received 27 June 2025
Accepted for publication 16 October 2025
Published 27 October 2025 Volume 2025:18 Pages 5529—5548
DOI https://doi.org/10.2147/IDR.S549854
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Hemant Joshi
Biao Yu,1,* Ying Wan,1,* Wenbo Ji,1 Juehui Mao,2 Runcong Zhang,3 Zhuowei Shen,4 Yimiao Hu,5 Heping Cai1
1Department of Pharmacy, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230000, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210000, People’s Republic of China; 3Department of Pharmacy, Changxing People’s Hospital, Changxing, Zhejiang, 313100, People’s Republic of China; 4Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Cardiothoracic Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, 236000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Heping Cai, Department of Pharmacy, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230000, People’s Republic of China, Email greenhprui@163.com
Purpose: Teicoplanin (TEC) is widely used for treating invasive infections caused by Gram-positive bacteria. Due to its high pharmacokinetic variability, several population pharmacokinetic (PPK) studies have been performed to identify factors contributing to the variability. This review aims to provide a comprehensive overview of published PPK studies and explore potential covariates.
Patients and Methods: We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates and probability of target attainment (PTA) against methicillin-resistant Staphylococcus aureus (MRSA).
Results: A total of eight PPK studies involving preterm infants, neonates, infants, children, and adolescents were finally included. The median weight-normalized clearance (CL) in adolescents was 0.0116 L/h/kg, 14.7% and 16.0% lower than that in infants and children, respectively, and significantly approximately 22.7% lower than that in neonates. Key covariates impacting TEC clearance included body weight, postmenstrual age (PMA), renal function parameters, albumin levels, and continuous kidney replacement therapy (CKRT) status. Monte Carlo simulations indicated that current dosing regimens may be inadequate, particularly when treating MRSA with minimum inhibitory concentration (MIC) = 2 mg/L, as the PTA for AUC24/MIC≥ 400 often fell below 90%.
Conclusion: TEC dosing in pediatric patients should be individualized, taking into account factors like age, weight, and renal function. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of TEC.
PROSPERO Registration: CRD420251012884
Keywords: teicoplanin, population pharmacokinetics, nonlinear mixed-effect model, dosage optimization, pediatric
1Department of Pharmacy, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230000, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210000, People’s Republic of China; 3Department of Pharmacy, Changxing People’s Hospital, Changxing, Zhejiang, 313100, People’s Republic of China; 4Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Cardiothoracic Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui, 236000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Heping Cai, Department of Pharmacy, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230000, People’s Republic of China, Email greenhprui@163.com
Purpose: Teicoplanin (TEC) is widely used for treating invasive infections caused by Gram-positive bacteria. Due to its high pharmacokinetic variability, several population pharmacokinetic (PPK) studies have been performed to identify factors contributing to the variability. This review aims to provide a comprehensive overview of published PPK studies and explore potential covariates.
Patients and Methods: We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates and probability of target attainment (PTA) against methicillin-resistant Staphylococcus aureus (MRSA).
Results: A total of eight PPK studies involving preterm infants, neonates, infants, children, and adolescents were finally included. The median weight-normalized clearance (CL) in adolescents was 0.0116 L/h/kg, 14.7% and 16.0% lower than that in infants and children, respectively, and significantly approximately 22.7% lower than that in neonates. Key covariates impacting TEC clearance included body weight, postmenstrual age (PMA), renal function parameters, albumin levels, and continuous kidney replacement therapy (CKRT) status. Monte Carlo simulations indicated that current dosing regimens may be inadequate, particularly when treating MRSA with minimum inhibitory concentration (MIC) = 2 mg/L, as the PTA for AUC24/MIC≥ 400 often fell below 90%.
Conclusion: TEC dosing in pediatric patients should be individualized, taking into account factors like age, weight, and renal function. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of TEC.
PROSPERO Registration: CRD420251012884
Keywords: teicoplanin, population pharmacokinetics, nonlinear mixed-effect model, dosage optimization, pediatric