Veterinary Sciences
·
2025
·Vol. 12
·期 4
·294
·
IF 2.3
Tiantian Gao,Xuesong Liu,Di Qiu,Yanan Li,Zongsheng Qiu,Jingjing Qi,Shuxin Li,Xiaoyan Guo,Yan Zhang,Ziqi Wang,Xiang Gao,Yuhui Ma,Tianwen Ma
Simple SummaryBacterial infection is a major cause of death in foals.Escherichia coli(E. coli) is a Gram-negative bacterium that causes sepsis, which can be life-threatening in horses. Cefquinome has broad-spectrum antimicrobial activity and is widely used in the treatment of animal diseases. At the same time, it is the fourth generation of cephalosporin antibiotics for veterinary use, and it has good antibacterial activity against both Gram-positive and Gram-negative bacteria. Cefquinome is utilized for the treatment of septicemia induced byE. coli, as well as respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, there is a lack of studies using cefquinome to targetE. colias a pathogen of sepsis. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is a fundamental step in semi-mechanical methodology aimed at improving dose planning of systemically active antimicrobial agents. PK/PD models can determine the relationship between drug concentration, antibacterial action, and time, deriving the most effective dosing regimen. This study was based on this model to verify the optimal dosing regimen forE. coliinfection in foals and to provide a theoretical basis for the precision treatment of foals.Cefquinome is used to treat septicemia caused byEscherichia coli(E. coli) and respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, studies reporting the use of cefquinome to targetE. colias pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome againstE. coliusing 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 (T1/2β) was 2.35 h, the area under the curve (AUC0–last) was 12.33 μg·h/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 μg/mL, the time to reach the maximum serum concentration (Tmax) was 2.16 h, T1/2βwas 4.16 h, AUC0–lastwas 5.41 μg·h/mL, MRT0–lastwas 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.
研究领域:
兽医学
·
微生物学
·
药物动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Yujuan Mao,Yumeng Chen,Chang Liu,Xingyue He,Yi Zheng,Xiaolan Chen,Ying Wang,Wei Chen,Yanling Wu,Yan Shen,Haifeng Yang,Songbo Ma
Introduction Cefquinome sulfate (CS) is the first fourth-generation antibiotic for animals, which has a wide antibacterial spectrum, strong antibacterial activity and low drug resistance. However, it is accompanied by problems of poor therapeutic efficacy. In this context, the use of nanosuspensions have been found to be an attractive strategy. The main objective of this work is to develop a new oily nanosuspension to improve bioavailability and stability of CS formulations.Methods After screening the formulations, cefquinome sulfate oily nanosuspension (CS-NSP) was prepared by mortar grinding, using propylene glycol dicaprolate/dicaprate (Labrafac™ PG) as oil medium and caprylocaproyl polyoxyl-8 glycerides (Labrasol®) as stabilizer. The properties of CS-NSP were investigated by testing its physicochemical characteristics, stability, in vitro release, hemolysis, and muscle irritation. The in vivo pharmacokinetics of CS-NSP was studied using rats.Results Results show that CS-NSP presents suitable stability, physicochemical properties and safety. Moreover, a rapid release and high bioavailability of CS-NSP have also been verified in the study. Pharmacokinetic experiments in vivo showed that the bioavailability of CS-NSP was about 1.6 times that of commercial cefquinome sulfate injection (CS-INJ, Chuangdao®) (p<0.01). These advantages of CS-NSP were carried out by small particle size and low viscosity, being associated with the use of Labrafac PG and stabilizer Labrasol.Conclusion The results proved that the new preparation is safe and effective and is expected to become a promising veterinary nanodelivery system.
研究领域:
兽医学
·
药剂学
·
纳米技术
✓ 已验证
DOI
高影响因子
JOURNAL OF MICROBIOLOGY
·
2021
·Vol. 59
·期 12
·1112-1124
·
IF 3.422
Gao Linglin,Zhu Hao,Chen Yun,Yang Yuhui
Cefquinome (CEQ) is a novel β-lactam antibiotic that exhibits excellent antibacterial activity against Staphylococcus aureus . However, the bacterial protein targets of CEQ are unclear. To evaluate the relationship between the pharmacokinetic/pharmacodynamic (PK/PD) parameters of CEQ and strains with varying degrees of resistance and to elucidate bacterial protein responses to CEQ treatment, label-free quantitative proteomics analysis was conducted. The sensitive S. aureus ATCC6538 and the resistant 2MIC and 8MIC were tested for differentially expressed proteins. An in vitro model was treated with different concentrations of CEQ (3, 5, or 10 µg/ml) with different terminal half-lives (2.5 or 5 h) at different intervals (12 or 24 h). Differentially expressed proteins were evaluated using Gene Ontology analysis followed by KEGG pathway enrichment analysis and STRING network analysis. RT-qPCR was performed to validate the differentially expressed proteins at the molecular level. The results showed that the degree of resistance increased in a cumulative manner and increased gradually with the extension of administration time. The resistant strain would not have appeared in the model only if %T > mutant prevention concentration ≥ 50%. The expression of 45 proteins significantly changed following CEQ treatment, among which 42 proteins were obviously upregulated and 3 were downregulated. GO analysis revealed that the differentially expressed proteins were mainly present on cells and the cell membrane, participated in metabolic and intracellular processes, and had catalytic and binding activities. The RPSO, SDHB, CITZ, ADK, and SAOUHSC 00113 genes in S. aureus may play important roles in the development of resistance to CEQ. These results provided important reference candidate proteins as targets for overcoming S. aureus resistance to CEQ.
研究领域:
微生物学
·
蛋白质组学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）