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已发表论文
抽动障碍儿童和青少年硫必利群体药代动力学：利用血浆和唾液浓度指导个体化给药
Authors Huang W , Shen J, Luo X, Wu Y, Zheng Y , Zhou J, Xu B , Yin X, Wu X
Received 8 December 2025
Accepted for publication 23 March 2026
Published 21 April 2026 Volume 2026:20 587387
DOI https://doi.org/10.2147/DDDT.S587387
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Wei Huang,1,2 Jianfeng Shen,1 Xin Luo,1,2 Yangrui Wu,1,2 You Zheng,1 Jianxing Zhou,3,4 Baohua Xu,1 Xiaorong Yin,5 Xuemei Wu1
1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Pharmacy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 5Department of Pediatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
Correspondence: Xiaorong Yin, Department of Pediatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email sunnyxrr@126.com Xuemei Wu, Department of Pharmacy, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email wuxuemei@fjmu.edu.cn
Introduction: This study aimed to develop population pharmacokinetic (PopPK) models of tiapride based on plasma and saliva concentration in pediatric patients with tic disorders (TD) and evaluate the feasibility of non-invasive therapeutic drug monitoring (TDM) for precision dosing.
Methods: A prospective study was conducted in 38 TD patients aged 5– 15 years. PopPK models of tiapride were sequentially developed using nonlinear mixed-effects modeling. Monte Carlo simulation was employed to optimize dosing regimens, and Bayesian maximum a posteriori (MAP) was applied to facilitate model-informed precision dosing (MIPD). The predictive performance of the established model was internally evaluated using saliva concentration.
Results: The PopPK model of tiapride using plasma concentration was best described by a one-compartment structure model. The typical estimates of the absorption rate constant (Ka), plasma clearance (CL/F), and volume of distribution (V/F) were 0.219 h− 1, 15.3 L/h, and 5.77 L, respectively. A plasma–saliva joint model was subsequently established, incorporating Michaelis-Menten nonlinear transport kinetics to characterize the drug distribution from plasma to saliva, with an estimated Michaelis-Menten constant (KM) of 762 ng/mL and a maximum transport rate (Vmax) of 34.7 mg/h. Saliva elimination was modeled as a first-order process. Fat-free mass (FFM) was identified as a significant covariate on both CL/F and saliva clearance (K30), scaled by power exponents of 0.553 and 0.38, respectively, relative to a reference FFM of 30.62 kg. Simulations based on the final model suggested that a dosing regimen of 75 mg administered three times daily (tid) is optimal for achieving target therapeutic concentration. MAP estimation confirmed that saliva concentration can reliably predict the systemic exposure of tiapride.
Conclusion: The PopPK models of tiapride enable MIPD in children and adolescents with TD and support saliva as a non-invasive matrix for TDM. Further prospective validation in independent pediatric cohorts is warranted before routine clinical implementation.
Keywords: tic disorders, tiapride, population pharmacokinetics, non-invasive sampling, therapeutic drug monitoring, model-informed precision dosing
1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Pharmacy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 5Department of Pediatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
Correspondence: Xiaorong Yin, Department of Pediatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email sunnyxrr@126.com Xuemei Wu, Department of Pharmacy, Fujian Medical University Union Hospital, 29 Xinquan Road, Gulou District, Fuzhou, Fujian, 350001, People’s Republic of China, Email wuxuemei@fjmu.edu.cn
Introduction: This study aimed to develop population pharmacokinetic (PopPK) models of tiapride based on plasma and saliva concentration in pediatric patients with tic disorders (TD) and evaluate the feasibility of non-invasive therapeutic drug monitoring (TDM) for precision dosing.
Methods: A prospective study was conducted in 38 TD patients aged 5– 15 years. PopPK models of tiapride were sequentially developed using nonlinear mixed-effects modeling. Monte Carlo simulation was employed to optimize dosing regimens, and Bayesian maximum a posteriori (MAP) was applied to facilitate model-informed precision dosing (MIPD). The predictive performance of the established model was internally evaluated using saliva concentration.
Results: The PopPK model of tiapride using plasma concentration was best described by a one-compartment structure model. The typical estimates of the absorption rate constant (Ka), plasma clearance (CL/F), and volume of distribution (V/F) were 0.219 h− 1, 15.3 L/h, and 5.77 L, respectively. A plasma–saliva joint model was subsequently established, incorporating Michaelis-Menten nonlinear transport kinetics to characterize the drug distribution from plasma to saliva, with an estimated Michaelis-Menten constant (KM) of 762 ng/mL and a maximum transport rate (Vmax) of 34.7 mg/h. Saliva elimination was modeled as a first-order process. Fat-free mass (FFM) was identified as a significant covariate on both CL/F and saliva clearance (K30), scaled by power exponents of 0.553 and 0.38, respectively, relative to a reference FFM of 30.62 kg. Simulations based on the final model suggested that a dosing regimen of 75 mg administered three times daily (tid) is optimal for achieving target therapeutic concentration. MAP estimation confirmed that saliva concentration can reliably predict the systemic exposure of tiapride.
Conclusion: The PopPK models of tiapride enable MIPD in children and adolescents with TD and support saliva as a non-invasive matrix for TDM. Further prospective validation in independent pediatric cohorts is warranted before routine clinical implementation.
Keywords: tic disorders, tiapride, population pharmacokinetics, non-invasive sampling, therapeutic drug monitoring, model-informed precision dosing