Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia

被引:1
|
作者
He, Yun-Ying [1 ]
Sun, Jing [1 ,2 ]
Wu, Yue-E [1 ]
Wang, Yong-Bin [3 ]
van den Anker, John [4 ,5 ,6 ,7 ,8 ,9 ]
Hao, Guo-Xiang [1 ,12 ]
Sun, De-Qing [2 ]
Zhao, Wei [1 ,2 ,10 ,11 ,12 ]
机构
[1] Shandong Univ, Dept Clin Pharm, Inst Clin Pharmacol, Key Lab Chem Biol,Minist Educ,NMPA Key Lab Clin Re, Jinan, Peoples R China
[2] Shandong Univ, Dept Pharm, Hosp 2, Jinan, Peoples R China
[3] Shandong Univ, Dept Resp, Hosp 2, Jinan, Peoples R China
[4] Childrens Natl Hosp, Div Clin Pharmacol, Washington, DC USA
[5] George Washington Univ, Dept Pediat, Sch Med & Hlth Sci, Washington, DC USA
[6] George Washington Univ, Sch Med & Hlth Sci, Dept Pharmacol & Physiol, Washington, DC USA
[7] George Washington Univ, Sch Med & Hlth Sci, Dept Genom, Washington, DC USA
[8] George Washington Univ, Sch Med & Hlth Sci, Dept Precis Med, Washington, DC USA
[9] Univ Basel, Univ Childrens Hosp Basel, Dept Paediat Pharmacol & Pharmacometr, Basel, Switzerland
[10] Shandong First Med Univ, Dept Clin Pharm, Clin Trial Ctr, Affiliated Hosp 1, Jinan, Shandong, Peoples R China
[11] Shandong Prov Qianfoshan Hosp, Shandong Engn & Technol Res Ctr Pediat Drug Dev, Med & Hlth Key Lab Clin Pharm, Jinan, Shandong, Peoples R China
[12] Shandong Univ, Dept Clin Pharm, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci,Cheeloo Coll Med, Jinan, Peoples R China
基金
国家重点研发计划;
关键词
dosing optimization; elderly; levofloxacin; population pharmacokinetics; COMMUNITY-ACQUIRED PNEUMONIA; 500; MG; PHARMACODYNAMICS; AGE; CIPROFLOXACIN; MULTICENTER; SAFETY;
D O I
10.1111/bcp.16003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims: Levofloxacin is a quinolone antibiotic with a broad antibacterial spectrum. It is frequently used in elderly patients with pneumonia. The pharmacokinetic profile of elderly patients changes with age, but data on the pharmacokinetics of levofloxacin in these patients are limited. The aim of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on this newly developed model. Methods: This is a prospective, open-label pharmacokinetic study in elderly patients with pneumonia. Blood samples were collected using an opportunistic approach. The plasma concentrations of levofloxacin were determined by high-performance liquid chromatography. A population pharmacokinetic model was established using nonlinear mixed-effect model software. Monte Carlo simulations were used for dose simulation and dose optimization. Results: Data from 51 elderly patients with pneumonia were used for the population pharmacokinetic analysis. A one-compartment model with first-order elimination was most suitable for describing the data, and the estimated glomerular filtration rate was the only covariate that had a significant impact on the model. The final model estimated that the mean clearance of levofloxacin in elderly patients with pneumonia was 5.26 L/h. Monte Carlo simulation results showed that the optimal dosing regimen for levofloxacin was 750 mg once a day in elderly patients with pneumonia, with a minimum inhibitory concentration of 2 mg/L. Conclusions: The population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.
引用
收藏
页码:1213 / 1221
页数:9
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