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Article

Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children

by 1,†, 2,†, 1,†, 3, 1, 1, 1, 1, 1 and 1,*
1
Department of Clinical Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
2
Department of Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
3
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Patrick J. Sinko
Pharmaceutics 2022, 14(5), 1033; https://doi.org/10.3390/pharmaceutics14051033
Received: 29 March 2022 / Revised: 26 April 2022 / Accepted: 9 May 2022 / Published: 11 May 2022
The present study aimed to establish population pharmacokinetic models of latamoxef, as well as its R- and S-epimers, and generate findings to guide the individualized administration of latamoxef in pediatric patients. A total of 145 in-hospital children aged 0.08–10.58 years old were included in this study. Three population pharmacokinetic models of latamoxef and its R- and S-epimers were established. The stability and predictive ability of the final models were evaluated by utilizing goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors. The final model of total latamoxef was considered as a basis for the dosing regimen. A two-compartment model with first-order elimination best described the pharmacokinetics of total latamoxef. The population typical values of total latamoxef were as follows: central compartment distribution volume (V1) of 4.84 L, peripheral compartment distribution volume (V2) of 16.18 L, clearance (CL) of 1.00 L/h, and inter-compartmental clearance (Q) of 0.97 L/h. Moreover, R-epimer has a higher apparent volume of distribution and lower clearance than S-epimer. Body surface area (BSA) was identified as the most significant covariate to V, CL, and Q. Specific recommendations are given for dosage adjustment in pediatric patients based on BSA. This study highlights that a BSA-normalized dose of latamoxef was required when treating different bacteria to reach the therapeutic target more effectively. View Full-Text
Keywords: latamoxef; epimer; population pharmacokinetics; dosing; children latamoxef; epimer; population pharmacokinetics; dosing; children
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MDPI and ACS Style

Wang, Y.; Sun, D.; Mei, Y.; Wu, S.; Li, X.; Li, S.; Wang, J.; Gao, L.; Xu, H.; Tuo, Y. Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children. Pharmaceutics 2022, 14, 1033. https://doi.org/10.3390/pharmaceutics14051033

AMA Style

Wang Y, Sun D, Mei Y, Wu S, Li X, Li S, Wang J, Gao L, Xu H, Tuo Y. Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children. Pharmaceutics. 2022; 14(5):1033. https://doi.org/10.3390/pharmaceutics14051033

Chicago/Turabian Style

Wang, Yang, Dan Sun, Yan Mei, Sanlan Wu, Xinlin Li, Sichan Li, Jun Wang, Liuliu Gao, Hua Xu, and Yali Tuo. 2022. "Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children" Pharmaceutics 14, no. 5: 1033. https://doi.org/10.3390/pharmaceutics14051033

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