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Journal of veterinary pharmacology and therapeutics2017; 40(6); 656-662; doi: 10.1111/jvp.12399

Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Abstract: Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 μg/ml (low dose) and 7.45 ± 1.05 μg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 μg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 μg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 μg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.
Publication Date: 2017-03-19 PubMed ID: 28317126DOI: 10.1111/jvp.12399Google Scholar: Lookup
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Summary

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The study examines the absorption, distribution, metabolism, and excretion of the antimicrobial drug ceftiofur sodium in pregnant horses. It finds that the drug doesn’t appear to significantly cross the fetal membranes, thus potentially limiting its antimicrobial efficacy in the fetus.

Study Design

  • The researchers worked with eleven pregnant pony mares, who were given ceftiofur sodium once a day, via intramuscular injections.
  • They were given one of two doses—either 2.2mg/kg or 4.4mg/kg.
  • The researchers collected plasma samples at several time points both before and after administering the antibiotic.
  • Eight mares were brought back into the study close to their expected foaling —the childbirth process in horses— dates.
  • These mares were also given daily doses of ceftiofur sodium to ensure steady concentrations of the drug at foaling time.
  • Parturition (childbirth) was induced in the mares using oxytocin, another hormone, one hour after antibiotic administration.
  • The researchers then collected a variety of samples, including allantoic and amniotic fluid, colostrum (the mare’s first milk), and placental tissues, as well as plasma samples from the foals themselves.

Results and Interpretation

  • The team used high-performance liquid chromatography to measure the concentration of desfuroylceftiofur acetamide (DCA), the active form of ceftiofur sodium, in their collected samples.
  • They noted that peak serum concentrations of DCA after administration were directly proportional to the dose—higher doses led to higher concentrations.
  • Additionally, the drug was metabolized and eliminated quicker after administration of the lower dose compared to the higher dose.
  • At the time of foaling, the researchers observed a mean serum DCA concentration within the mares, and also detected a mean concentration in the colostrum.
  • However, DCA concentrations in allantoic and amniotic fluid, placental tissues, and the foals’ plasma were consistently below the limit of quantification, suggesting that the drug was not being efficiently transferred across the fetal membranes.

Conclusion

  • The results of the study suggest that the administration of ceftiofur sodium may not effectively safeguard foals, as the drug appears to have difficulty crossing the fetal membranes.
  • This implies a potential limitation in achieving antimicrobial efficacy against pathogens in the fetus when administering ceftiofur sodium to pregnant mares.

Cite This Article

APA
Macpherson ML, Giguère S, Pozor MA, Runcan E, Vickroy TW, Benson SA, Troedsson MHT, Hatzel JN, Larson J, Vanden Berg E, Kelleman AA, Sanchez LC, LeBlanc MM. (2017). Pharmacokinetics of ceftiofur sodium in equine pregnancy. J Vet Pharmacol Ther, 40(6), 656-662. https://doi.org/10.1111/jvp.12399

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 40
Issue: 6
Pages: 656-662

Researcher Affiliations

Macpherson, M L
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Giguère, S
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Pozor, M A
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Runcan, E
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Vickroy, T W
  • Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Benson, S A
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Troedsson, M H T
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Hatzel, J N
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Larson, J
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Vanden Berg, E
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Kelleman, A A
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Sanchez, L C
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
LeBlanc, M M
  • Rood and Riddle Equine Hospital, Lexington, KY, USA.

MeSH Terms

  • Allantois / chemistry
  • Amniotic Fluid / chemistry
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Cephalosporins / administration & dosage
  • Cephalosporins / analysis
  • Cephalosporins / blood
  • Cephalosporins / pharmacokinetics
  • Colostrum / chemistry
  • Female
  • Fetus / chemistry
  • Half-Life
  • Horses / metabolism
  • Injections, Intramuscular / veterinary
  • Labor, Induced / veterinary
  • Placenta / chemistry
  • Pregnancy / metabolism

Citations

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