Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses.
Abstract: The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125-2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration-time curves (AUC) of cefquinome showed a dose-dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half-life values (2.30-2.41 h), the mean residence time (1.77-2.25 h), the systemic clearance (158-241 mL/h/kg), and the volume of distribution at steady-state (355-431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUC /AUC ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12-h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.
© 2016 John Wiley & Sons Ltd.
Publication Date: 2016-09-18 PubMed ID: 27641837DOI: 10.1111/jvp.12362Google Scholar: Lookup
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- Journal Article
Summary
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The research investigated the pharmacokinetics of the antibiotic cefquinome in horses’ blood and synovial fluid after administering several doses. The study aimed to examine the safety and measure the drug’s presence over time in these body fluids.
Study Design and Methods
- The study included sixteen healthy horses. The horses were divided into four groups, with each group receiving different doses of the drug cefquinome.
- The doses administered were 1, 2, 4, and 6 mg/kg every 12 hours over seven days, equating to 13 injections in total.
- The researchers collected blood and synovial fluid samples 12 hours following the administration of the first and final doses.
- The samples were then analyzed using a process called high-performance liquid chromatography, used to identify the components in the collected samples.
Results and Findings
- The quantities of cefquinome in the plasma and synovial fluid and the area under the concentration-time curves (AUC) showed a dose-dependent increase, meaning higher doses resulted in larger concentrations of the drug.
- The average plasma half-life of cefquinome ranged between 2.30-2.41 hours. This value refers to how long it takes for the concentration of the drug in the body to decrease by half.
- The systemic clearance rate was determined to be 158-241 mL/h/kg, indicating the body’s efficiency in eliminating the drug.
- Cefquinome did not accumulate after multiple doses, signaling the body effectively eliminated it with each dose.
- The AUC ratio (which compares drug availability in plasma and synovial fluid) demonstrated that cefquinome easily penetrated the synovial fluid.
Conclusions and Recommendations
- Cefquinome was well-tolerated by the horses, with no adverse effects observed.
- The percentage of time that the plasma concentrations were above the Minimum Inhibitory Concentration (MIC) – the lowest concentration required to inhibit bacterial growth – was greater than 45% for bacteria with MIC values of 0.25, 0.5, and 1 μg/mL after each respective dosage.
- Finally, the study concluded that further research is needed to determine the ideal dosage regimen for critically ill patients.
Cite This Article
APA
Uney K, Altan F, Altan S, Erol H, Arican M, Elmas M.
(2016).
Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses.
J Vet Pharmacol Ther, 40(3), 239-247.
https://doi.org/10.1111/jvp.12362 Publication
Researcher Affiliations
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey.
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Dicle, Diyarbakir, Turkey.
- Department of Surgery, Faculty of Veterinary Medicine, University of Dicle, Diyarbakir, Turkey.
- Department of Surgery, Faculty of Veterinary Medicine, University of Erciyes, Kayseri, Turkey.
- Department of Surgery, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey.
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey.
MeSH Terms
- Animals
- Area Under Curve
- Cephalosporins / pharmacokinetics
- Dose-Response Relationship, Drug
- Horses / metabolism
- Synovial Fluid / chemistry
- Synovial Fluid / metabolism
Citations
This article has been cited 5 times.- Liu C, Han M, Wang H, Chen X, Tang Y, Zhang D, Li X, Liu Y. Elimination of Cefquinome Sulfate Residue in Cow's Milk after Intrauterine Infusion. Metabolites 2023 Mar 29;13(4).
- Totten KMC, Cunningham SA, Gades NM, Etzioni A, Patel R. Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits. Front Pharmacol 2022;13:840165.
- 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 Oct 28;13(11).
- 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 Oct 15;51(1):131.
- Li S, Yu N, Tang Y, Liu C, Zhang Y, Chen X, Wu H, Li X, Liu Y. Pharmacokinetics and relative bioavailability study of two cefquinome sulfate intramammary infusions in cow milk. Front Vet Sci 2024;11:1384076.
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