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Ex Vivo Pharmacokinetic/Pharmacodynamic Integration Model of Cefquinome Against Escherichia coli in Foals

文献类型： 外文期刊

作者： Gao, Tiantian 1 ; Liu, Xuesong 2 ; Qiu, Di 1 ; Li, Yanan 1 ; Qiu, Zongsheng 1 ; Qi, Jingjing 1 ; Li, Shuxin 1 ; Guo, Xiaoyan 1 ; Zhang, Yan 2 ; Wang, Ziqi 3 ; Gao, Xiang 1 ; Ma, Yuhui 4 ; Ma, Tianwen 1 ;

作者机构： 1.Northeast Agr Univ, Coll Vet Med, Heilongjiang Key Lab Lab Anim & Comparat Med, Coll Vet Med, Harbin 150030, Peoples R China

2.Vet Heilongjiang Acad Agr Sci, Branch Anim Husb, Heilongjiang Prov Key Lab Vet Drugs, XL, Qiqihar 161005, Peoples R China

3.Feihe Qiqihar Dairy Co Ltd, Qiqihar 161000, Peoples R China

4.Xinjiang Zhaosu Cty Xiyu Horse Ind Co Ltd, Zhaosu 835699, Peoples R China

关键词： cefquinome; Escherichia coli; PK/PD model; dose regimen

期刊名称：VETERINARY SCIENCES （ 影响因子：2.3； 五年影响因子：2.4 ）

ISSN：

年卷期： 2025 年 12 卷 4 期

页码：

收录情况： SCI

摘要： Cefquinome is used to treat septicemia caused by Escherichia coli (E. coli) and respiratory infections caused by Streptococcus equi subsp. zooepidemicus in foals. However, studies reporting the use of cefquinome to target E. coli as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against E. coli using a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). The main pharmacokinetic parameters of cefquinome in foals were as follows: after intravenous administration, the elimination half-life (T1/2 beta) was 2.35 h, the area under the curve (AUC0-last) was 12.33 mu gh/mL, the mean residence time (MRT0-last) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (Cmax) was 0.89 mu g/mL, the time to reach the maximum serum concentration (Tmax) was 2.16 h, T1/2 beta was 4.16 h, AUC0-last was 5.41 mu gh/mL, MRT0-last was 4.92 h, CL was 0.15 L/h/kg, and the absolute bioavailability (F) was 43.86%. An inhibitory sigmoid Emax model was used to integrate the PK/PD indices with ex vivo antimicrobial effects to identify pharmacodynamic targets (PDTs). According to the dose calculation formula, the doses of intramuscularly administered cefquinome required to achieve bacteriostatic effects, bactericidal effects, and bactericidal elimination were 1.10, 1.66, and 2.28 mg/kg, respectively. However, further studies are warranted to verify the therapeutic efficacy of cefquinome in clinical settings.

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