FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Vet Sci / Ex Vivo Pharmacokinetic/Pharmacodynamic Integration Model of...
Veterinary sciences2025; 12(4); 294; doi: 10.3390/vetsci12040294

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

Abstract: Cefquinome is used to treat septicemia caused by () and respiratory infections caused by subsp. in foals. However, studies reporting the use of cefquinome to target as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against 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 (T) was 2.35 h, the area under the curve (AUC) was 12.33 μg·h/mL, the mean residence time (MRT) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (C) was 0.89 μg/mL, the time to reach the maximum serum concentration (T) was 2.16 h, T was 4.16 h, AUC was 5.41 μg·h/mL, MRT 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.
Get Full Text
Publication Date: 2025-03-22 PubMed ID: 40284796PubMed Central: PMC12031376DOI: 10.3390/vetsci12040294Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The researchers study the use of the drug Cefquinome in foals for the treatment of septicemia and respiratory infections caused by Escherichia coli. They use a pharmacokinetic/pharmacodynamic (PK/PD) model to find the optimal dosage and examine its antimicrobial effects.

Study Design and Approach

  • The researchers aimed to find the optimal dosage regimen for Cefquinome, a drug used to treat Escherichia coli infections in foals. This was done using a PD/PK integration model.
  • 1mg/kg of Cefquinome was administered to the foals either intramuscularly or intravenously, and blood samples were collected to measure the concentration of the drug over time using high-performance liquid chromatography (HPLC).
  • Using a software called WinNonlin, the pharmacokinetic parameters of Cefquinome were evaluated. These parameters included the elimination half-life (T), the area under the serum concentration-time curve (AUC), the mean residence time (MRT), and the clearance rate (CL).

Key Findings and Observations

  • Following intravenous administration, the researchers determined the elimination half-life to be 2.35 hours, the area under the curve as 12.33 μg·h/mL, the mean residence time as 2.67 hours, and the clearance rate as 0.09 L/h/kg.
  • After intramuscular administration, the peak concentration was found to be 0.89 μg/mL, the time to reach the maximum serum concentration as 2.16 hours. The elimination half-life was discovered to be 4.16 hours, AUC as 5.41 μg·h/mL, MRT as 4.92 hours, CL as 0.15 L/h/kg, and the absolute bioavailability as 43.86%.
  • To identify pharmacodynamic targets, an inhibitory sigmoid Emax model was used. This process integrated the previously recorded PK/PD parameters with the drug’s ex vivo antimicrobial effects.
  • As per the dose calculation formula, bacteriostatic effects were achieved with a dose of 1.10 mg/kg, bactericidal effects were attained at 1.66 mg/kg, and bactericidal elimination was seen at 2.28 mg/kg, all of which were administered intramuscularly. But, further research is required to confirm the therapeutic efficacy of Cefquinome in a clinical setting.

Cite This Article

APA
Gao T, Liu X, Qiu D, Li Y, Qiu Z, Qi J, Li S, Guo X, Zhang Y, Wang Z, Gao X, Ma Y, Ma T. (2025). Ex Vivo Pharmacokinetic/Pharmacodynamic Integration Model of Cefquinome Against Escherichia coli in Foals. Vet Sci, 12(4), 294. https://doi.org/10.3390/vetsci12040294

Publication

Veterinary sciences
ISSN: 2306-7381
NlmUniqueID: 101680127
Country: Switzerland
Language: English
Volume: 12
Issue: 4
PII: 294

Researcher Affiliations

Gao, Tiantian
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Liu, Xuesong
  • Heilongjiang Province Key Laboratory of Veterinary Drugs, Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar 161005, China.
Qiu, Di
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Li, Yanan
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Qiu, Zongsheng
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Qi, Jingjing
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Li, Shuxin
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Guo, Xiaoyan
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Zhang, Yan
  • Heilongjiang Province Key Laboratory of Veterinary Drugs, Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar 161005, China.
Wang, Ziqi
  • Feihe (Qiqihar) Dairy Co., Ltd., Qiqihar 161000, China.
Gao, Xiang
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Ma, Yuhui
  • Zhaosu County Xiyu Horse Industry Co., Ltd., Zhaosu County, Yili 835699, China.
Ma, Tianwen
  • Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
  • Zhaosu County Xiyu Horse Industry Co., Ltd., Zhaosu County, Yili 835699, China.

Grant Funding

  • 32402967 and 32402966 / National Natural Science Foundation of China
  • YQ2023C015 / Heilongjiang Provincial Natural Science Foundation

Conflict of Interest Statement

Author Ziqi Wang was employed by the company Feihe (Qiqihar) Dairy Co., Ltd.; Author Yuhui Ma and Tianwen Ma was employed by the company Zhaosu County Xiyu Horse Industry Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 39 references
  1. Willis AT, Magdesian KG, Byrne BA, Edman JM. Enterococcus infections in foals. Vet. J. 2019;248:42–47.
    doi: 10.1016/j.tvjl.2019.04.005pubmed: 31113561google scholar: lookup
  2. Grondahl G, Sternberg S, Jensen-Waern M, Johannisson A. Opsonic capacity of foal serum for the two neonatal pathogens Escherichia coli and Actinobacillus equuli. Equine Vet. J. 2001;33:670–675.
    doi: 10.2746/042516401776249381pubmed: 11770988google scholar: lookup
  3. Maddox TW, Clegg PD, Williams NJ, Pinchbeck GL. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance. Equine Vet. J. 2015;47:756–765.
    doi: 10.1111/evj.12471pubmed: 26084443google scholar: lookup
  4. Mao Y, Chen Y, Liu C, He X, Zheng Y, Chen X, Wang Y, Chen W, Wu Y, Shen Y. Cefquinome Sulfate Oily Nanosuspension Designed for Improving its Bioavailability in the Treatment of Veterinary Infections. Int. J. Nanomed. 2022;17:2535–2553.
    doi: 10.2147/IJN.S348822pmc: PMC9169852pubmed: 35677677google scholar: lookup
  5. Shantier SW. Review on the Characteristic, Properties and Analytical Methods of Cefquinomesulphate: Ss-lactam Veterinary Drug. Infect. Disord. Drug Targets 2020;20:27–32.
    doi: 10.2174/1871526518666181001122010pubmed: 30277168google scholar: lookup
  6. Gao L, Zhu H, Chen Y, Yang Y. Antibacterial pathway of cefquinome against Staphylococcus aureus based on label-free quantitative proteomics analysis. J. Microbiol. 2021;59:1112–1124.
    doi: 10.1007/s12275-021-1201-xpubmed: 34751907google scholar: lookup
  7. El-Tahawy AO, Said AA, Shams GA, Hassan HM, Hassan AM, Amer SA, El-Nabtity SM. Evaluation of cefquinome’s efficacy in controlling avian colibacillosis and detection of its residues using high performance liquid chromatography (HPLC). Saudi J. Biol. Sci. 2022;29:3502–3510.
    doi: 10.1016/j.sjbs.2022.02.029pmc: PMC9280232pubmed: 35844377google scholar: lookup
  8. Lee DH, Birhanu BT, Lee EB, Lee SJ, Boby N, Park YS, Park SC. Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals. Vet. Res. 2020;51:131.
    doi: 10.1186/s13567-020-00853-2pmc: PMC7566116pubmed: 33059768google scholar: lookup
  9. Dunkel B, Johns IC. Antimicrobial use in critically ill horses. J. Veter Emerg. Crit. Care. 2015;25:89–100.
    doi: 10.1111/vec.12275pubmed: 25582245google scholar: lookup
  10. Toutain PL, Pelligand L, Lees P, Bousquet-Melou A, Ferran AA, Turnidge JD. The pharmacokinetic/pharmacodynamic paradigm for antimicrobial drugs in veterinary medicine: Recent advances and critical appraisal. J. Vet. Pharmacol. Ther. 2021;44:172–200.
    doi: 10.1111/jvp.12917pubmed: 33089523google scholar: lookup
  11. Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K. Rational dosage regimens for cephalothin and cefazolin using pharmacokinetics and pharmacodynamics analysis in healthy horses. Equine Vet. J. 2021;53:1239–1249.
    doi: 10.1111/evj.13406pmc: PMC8518962pubmed: 33341979google scholar: lookup
  12. Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. J. Vet. Pharmacol. Ther. 2004;27:467–477.
    doi: 10.1111/j.1365-2885.2004.00613.xpubmed: 15601441google scholar: lookup
  13. Xiao X, Chen X, Yan K, Jiang L, Li R, Liu Y, Wang M, Wang Z. PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli. J. Vet. Pharmacol. Ther. 2022;45:83–91.
    doi: 10.1111/jvp.13012pubmed: 34469000google scholar: lookup
  14. Toutain PL, Bousquet-Melou A, Martinez M. AUC/MIC: A PK/PD index for antibiotics with a time dimension or simply a dimensionless scoring factor?. J. Antimicrob. Chemother. 2007;60:1185–1188.
    doi: 10.1093/jac/dkm360pubmed: 17932075google scholar: lookup
  15. Soto SM. Antibiotic Resistance in Bacterial Pathogens. Antibiotics 2023;12:451.
    doi: 10.3390/antibiotics12030451pmc: PMC10044665pubmed: 36978318google scholar: lookup
  16. Wilson A, Mair T, Williams N, McGowan C, Pinchbeck G. Antimicrobial prescribing and antimicrobial resistance surveillance in equine practice. Equine Vet. J. 2023;55:494–505.
    doi: 10.1111/evj.13587pubmed: 35575046google scholar: lookup
  17. Xiao X, Sun J, Chen Y, Huang RJ, Huang T, Qiao GG, Zhou YF, Liu YH. In vitro dynamic pharmacokinetic/pharmacodynamic(PK/PD) modeling and PK/PD cutoff of cefquinome against Haemophilus parasuis. BMC Vet. Res. 2015;11:33.
    doi: 10.1186/s12917-015-0343-7pmc: PMC4350951pubmed: 25889187google scholar: lookup
  18. Xiong M, Wu X, Ye X, Zhang L, Zeng S, Huang Z, Wu Y, Sun J, Ding H. Relationship between Cefquinome PK/PD Parameters and Emergence of Resistance of Staphylococcus aureus in Rabbit Tissue-Cage Infection Model. Front. Microbiol. 2016;7:874.
    doi: 10.3389/fmicb.2016.00874pmc: PMC4896111pubmed: 27375594google scholar: lookup
  19. Zhang BX, Lu XX, Gu XY, Li XH, Gu MX, Zhang N, Shen XG, Ding HZ. Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids. Vet. J. 2014;199:399–405.
    doi: 10.1016/j.tvjl.2013.12.015pubmed: 24423605google scholar: lookup
  20. Cheng P, Feng T, Zhang Y, Li X, Tian L, Wu J, Cheng F, Zeng Y, Chen H, He X. Comparative pharmacokinetics of intravenous and intramuscular cefquinome sulfate administration in ducklings and goslings. Am. J. Vet. Res. 2020;81:837–877.
    doi: 10.2460/ajvr.81.11.873pubmed: 33107745google scholar: lookup
  21. Xie W, Zhang X, Wang T, Du S. Pharmacokinetic analysis of cefquinome in healthy chickens. Br. Poult. Sci. 2013;54:81–86.
    pubmed: 23444857
  22. Zhang B, Gu X, Li X, Gu M, Zhang N, Shen X, Li Y, Ding H. Pharmacokinetics and ex-vivo pharmacodynamics of cefquinome against Klebsiella pneumonia in healthy dogs. J. Vet. Pharmacol. Ther. 2014;37:367–373.
    doi: 10.1111/jvp.12100pubmed: 24372291google scholar: lookup
  23. Zhao DH, Wang XF, Wang Q, Li LD. Pharmacokinetics, bioavailability and dose assessment of Cefquinome against Escherichia coli in black swans (Cygnus atratus). BMC Vet. Res. 2017;13:226.
    pmc: PMC5534040pubmed: 28754112
  24. Corum O, Yildiz R, Ider M, Altan F, Ok M, Uney K. Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves. J. Vet. Pharmacol. Ther. 2019;42:632–639.
    pubmed: 31197850
  25. Winther L, Baptiste KE, Friis C. Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part III. cefquinome. J. Vet. Pharmacol. Ther. 2011;34:482–486.
    pubmed: 21083664
  26. Li XB, Wu WX, Su D, Wang ZJ, Jiang HY, Shen JZ. Pharmacokinetics and bioavailability of cefquinome in healthy piglets. J. Vet. Pharmacol. Ther. 2008;31:523–527.
    pubmed: 19000274
  27. Elbadawy M, Soliman A, Abugomaa A, Alkhedaide A, Soliman MM, Aboubakr M. Disposition of Cefquinome in Turkeys (Meleagris gallopavo) Following Intravenous and Intramuscular Administration. Pharmaceutics 2021;13:1804.
    doi: 10.3390/pharmaceutics13111804pmc: PMC8622898pubmed: 34834219google scholar: lookup
  28. Altayban A, Kandeel M, Kitade Y, Al-Nazawi M. A pilot study on the pharmacokinetics of a single intramuscular injection of cefquinome in Arabian camel calves. Acta Vet. Hung. 2020;68:59–64.
    pubmed: 32384074
  29. Shan Q, Yang F, Wang J, Ding H, He L, Zeng Z. Pharmacokinetic/pharmacodynamic relationship of cefquinome against Pasteurella multocida in a tissue-cage model in yellow cattle. J. Vet. Pharmacol. Ther. 2014;37:178–185.
    doi: 10.1111/jvp.12076pubmed: 23980645google scholar: lookup
  30. Qiu Z, Cao C, Qu Y, Lu Y, Sun M, Zhang Y, Zhong J, Zeng Z. In vivo activity of cefquinome against Riemerella anatipestifer using the pericarditis model in the duck. J. Vet. Pharmacol. Ther. 2016;39:299–304.
    pubmed: 26560807
  31. Elazab ST, Schrunk DE, Griffith RW, Ensley SM, Dell’Anna G, Mullin K, Elsayed MG, Amer MS, El-Nabtity SM, Hsu WH. Pharmacokinetics of cefquinome in healthy and Pasteurella multocida-infected rabbits. J. Vet. Pharmacol. Ther. 2018;41:374–377.
    doi: 10.1111/jvp.12489pubmed: 29383736google scholar: lookup
  32. Venkatachalam D, Dumka VK, Ranjan B. Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves. J. Vet. Pharmacol. Ther. 2018;41:155–158.
    doi: 10.1111/jvp.12451pubmed: 28891215google scholar: lookup
  33. Uney K, Altan F, Elmas M. Development and validation of a high-performance liquid chromatography method for determination of cefquinome concentrations in sheep plasma and its application to pharmacokinetic studies. Antimicrob. Agents Chemother. 2011;55:854–859.
    doi: 10.1128/AAC.01126-10pmc: PMC3028820pubmed: 21098247google scholar: lookup
  34. Yang Q, Liu X, Zhang C, Yong K, Clifton AC, Ding H, Liu Y. Pharmacokinetics and Pharmacodynamics of Gamithromycin Treatment of Pasteurella multocida in a Murine Lung Infection Model. Front. Pharmacol. 2019;10:1090.
    doi: 10.3389/fphar.2019.01090pmc: PMC6798029pubmed: 31680940google scholar: lookup
  35. Toutain PL, Potter T, Pelligand L, Lacroix M, Illambas J, Lees P. Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: The case of tulathromycin in the calf. J. Vet. Pharmacol. Ther. 2017;40:16–27.
    doi: 10.1111/jvp.12333pubmed: 27501187google scholar: lookup
  36. Toutain PL, Bousquet-Melou A, Damborg P, Ferran AA, Mevius D, Pelligand L, Veldman KT, Lees P. En Route towards European Clinical Breakpoints for Veterinary Antimicrobial Susceptibility Testing: A Position Paper Explaining the VetCAST Approach. Front. Microbiol. 2017;8:2344.
    pmc: PMC5736858pubmed: 29326661
  37. Ahmad I, Hao H, Huang L, Sanders P, Wang X, Chen D, Tao Y, Xie S, Xiuhua K, Li J. Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle. Front. Microbiol. 2015;6:588.
    doi: 10.3389/fmicb.2015.00588pmc: PMC4470083pubmed: 26136730google scholar: lookup
  38. Tong YC, Li PC, Yang Y, Lin QY, Liu JT, Gao YN, Zhang YN, Jin S, Qing SZ, Xing FS. Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli. Int. J. Mol. Sci. 2023;24:9627.
    doi: 10.3390/ijms24119627pmc: PMC10253432pubmed: 37298578google scholar: lookup
  39. Mi K, Li M, Sun L, Hou Y, Zhou K, Hao H, Pan Y, Liu Z, Xie C, Huang L. Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs. Antibiotics 2021;10:958.
    doi: 10.3390/antibiotics10080958pmc: PMC8389024pubmed: 34439008google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.