caa a22 4500 605533717 CHVBK 20210128100839.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s10928-014-9396-7 doi (NATIONALLICENCE)springer-10.1007/s10928-014-9396-7 In vitro simulation of in vivo pharmacokinetic model with intravenous administration via flow rate modulation [Elektronische Daten] [Yuan-cheng Chen, Wang Liang, Jia-li Hu, Gao-li He, Xiao-jie Wu, Xiao-fang Liu, Jing Zhang, Xue-qian Hu] The aim of this paper was to propose a method of flow rate modulation for simulation of in vivo pharmacokinetic (PK) model with intravenous injection based on a basic in vitro PK model. According to the rule of same relative change rate of concentration per unit time in vivo and in vitro, the equations for flow rate modulation were derived using equation method. Four examples from literature were given to show the application of flow rate modulation in the simulation of PK model of antimicrobial agents in vitro. Then an experiment was performed to confirm the feasibility of flow rate modulation method using levo-ornidazole as an example. The accuracy and precision of PK simulations were evaluated using average relative deviation (ARD), mean error and root mean squared error. In vitro model with constant flow rate could mimic one-compartment model, while the in vitro model with decreasing flow rate could simulate the linear mammillary model with multiple compartments. Zero-order model could be simulated using the in vitro model with elevating flow rate. In vitro PK model with gradually decreasing flow rate reproduced the two-compartment kinetics of levo-ornidazole quite well. The ARD was 0.925% between in vitro PK parameters and in vivo values. Results suggest that various types of PK model could be simulated using flow rate modulation method without modifying the structure. The method provides uniform settings for the simulation of linear mammillary model and zero-order model based on in vitro one-compartment model, and brings convenience to the pharmacodynamic study. Springer Science+Business Media New York, 2014 In vitro model nationallicence Pharmacokinetic simulation nationallicence Flow rate modulation nationallicence Equation method nationallicence Intravenous injection nationallicence Chen Yuan-cheng Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Liang Wang Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Hu Jia-li Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut He Gao-li Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Wu Xiao-jie Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Liu Xiao-fang Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Zhang Jing Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut Hu Xue-qian Department of Pharmacy, Tongren Hospital Affiliated to Medical College of Shanghai Jiaotong University, 200336, Shanghai, China aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/1(2015-02-01), 33-43 1567-567X 42:1<33 2015 42 10928 https://doi.org/10.1007/s10928-014-9396-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-014-9396-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Yuan-cheng Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Liang Wang Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Hu Jia-li Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- He Gao-li Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Wu Xiao-jie Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Liu Xiao-fang Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Zhang Jing Institute of Antibiotics, Huashan Hospital, Fudan University, 200040, Shanghai, China aut NATIONALLICENCE 700 1- Hu Xue-qian Department of Pharmacy, Tongren Hospital Affiliated to Medical College of Shanghai Jiaotong University, 200336, Shanghai, China aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/1(2015-02-01), 33-43 1567-567X 42:1<33 2015 42 10928