Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular administration of ceftiofur crystalline free acid to mares

D. Scofield, J. Black, Luke Anthony Wittenburg, D. Gustafson, R. Ferris, J. Hatzel, J. Traub-Dargatz, P. Mccue

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Reasons for performing study: Systemic administration of ceftiofur crystalline free acid (CCFA) may be a potential treatment for infectious endometritis caused by Streptococcus equi ssp. zooepidemicus (S.zooepidemicus) and other susceptible bacterial organisms in the mare. Objective: To determine if i.m. administration of CCFA at the label dose will exceed the minimum inhibitory concentration (MIC) of S.zooepidemicus in the endometrium following single administration and multiple administration protocols. Study design: Experimental pharmacokinetic study. Methods: Three mares (Group 1) were administered a single i.m. dose of CCFA (6.6mg/kg bwt) and blood and endometrial biopsies were collected at selected intervals for 144h. Six additional mares (Groups 2 and 3) received CCFA at times 0, 4, 11 and 18 days, and were sampled at predetermined times for 25 or 49 days, respectively. Plasma and tissue samples were analysed by high-pressure liquid chromatography with tandem mass spectrometry for desfuroylceftiofur acetamide concentration, which is a direct measure of all ceftofur and ceftiofur metabolites in the sample. Results: A mean plasma desfuroylceftiofur acetamide concentration of 0.367 ± 0.0162μg/ml (mean ± s.e.) was detected at 96h following administration. Mean endometrial tissue concentration was 0.510 ± 0.0418μg/g at 96h and exceeded the MIC for S.zooepidemicus (0.25μg/ml) throughout the 144h monitoring period for Group 1. Mares in Groups 2 and 3, given multiple doses of CCFA, maintained plasma concentrations above the MIC for S.zooepidemicus for 25 days. Endometrial tissue levels remained above the MIC at most data collection points for 25 days. Conclusions: Ceftiofur crystalline free acid reaches appropriate endometrial tissue values to exceed the MIC of S.zooepidemicus, a common cause of bacterial endometritis. Therefore, CCFA should be effective in the treatment of equine bacterial endometritis caused by S.zooepidemicus and other susceptible bacterial pathogens in the mare.

Original languageEnglish (US)
Pages (from-to)606-610
Number of pages5
JournalEquine Veterinary Journal
Volume46
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

ceftiofur
intramuscular injection
blood plasma
mares
metabolites
Microbial Sensitivity Tests
minimum inhibitory concentration
Acids
acids
Endometritis
endometritis
acetamides
dosage
Streptococcus equi
tissues
endometrium
Endometrium
Tandem Mass Spectrometry
pharmacokinetics
Horses

Keywords

  • Ceftiofur crystalline free acid
  • Endometritis
  • Horse
  • Mare
  • Therapy

ASJC Scopus subject areas

  • Equine
  • Medicine(all)

Cite this

Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular administration of ceftiofur crystalline free acid to mares. / Scofield, D.; Black, J.; Wittenburg, Luke Anthony; Gustafson, D.; Ferris, R.; Hatzel, J.; Traub-Dargatz, J.; Mccue, P.

In: Equine Veterinary Journal, Vol. 46, No. 5, 2014, p. 606-610.

Research output: Contribution to journalArticle

Scofield, D. ; Black, J. ; Wittenburg, Luke Anthony ; Gustafson, D. ; Ferris, R. ; Hatzel, J. ; Traub-Dargatz, J. ; Mccue, P. / Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular administration of ceftiofur crystalline free acid to mares. In: Equine Veterinary Journal. 2014 ; Vol. 46, No. 5. pp. 606-610.
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abstract = "Reasons for performing study: Systemic administration of ceftiofur crystalline free acid (CCFA) may be a potential treatment for infectious endometritis caused by Streptococcus equi ssp. zooepidemicus (S.zooepidemicus) and other susceptible bacterial organisms in the mare. Objective: To determine if i.m. administration of CCFA at the label dose will exceed the minimum inhibitory concentration (MIC) of S.zooepidemicus in the endometrium following single administration and multiple administration protocols. Study design: Experimental pharmacokinetic study. Methods: Three mares (Group 1) were administered a single i.m. dose of CCFA (6.6mg/kg bwt) and blood and endometrial biopsies were collected at selected intervals for 144h. Six additional mares (Groups 2 and 3) received CCFA at times 0, 4, 11 and 18 days, and were sampled at predetermined times for 25 or 49 days, respectively. Plasma and tissue samples were analysed by high-pressure liquid chromatography with tandem mass spectrometry for desfuroylceftiofur acetamide concentration, which is a direct measure of all ceftofur and ceftiofur metabolites in the sample. Results: A mean plasma desfuroylceftiofur acetamide concentration of 0.367 ± 0.0162μg/ml (mean ± s.e.) was detected at 96h following administration. Mean endometrial tissue concentration was 0.510 ± 0.0418μg/g at 96h and exceeded the MIC for S.zooepidemicus (0.25μg/ml) throughout the 144h monitoring period for Group 1. Mares in Groups 2 and 3, given multiple doses of CCFA, maintained plasma concentrations above the MIC for S.zooepidemicus for 25 days. Endometrial tissue levels remained above the MIC at most data collection points for 25 days. Conclusions: Ceftiofur crystalline free acid reaches appropriate endometrial tissue values to exceed the MIC of S.zooepidemicus, a common cause of bacterial endometritis. Therefore, CCFA should be effective in the treatment of equine bacterial endometritis caused by S.zooepidemicus and other susceptible bacterial pathogens in the mare.",
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AU - Wittenburg, Luke Anthony

AU - Gustafson, D.

AU - Ferris, R.

AU - Hatzel, J.

AU - Traub-Dargatz, J.

AU - Mccue, P.

PY - 2014

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N2 - Reasons for performing study: Systemic administration of ceftiofur crystalline free acid (CCFA) may be a potential treatment for infectious endometritis caused by Streptococcus equi ssp. zooepidemicus (S.zooepidemicus) and other susceptible bacterial organisms in the mare. Objective: To determine if i.m. administration of CCFA at the label dose will exceed the minimum inhibitory concentration (MIC) of S.zooepidemicus in the endometrium following single administration and multiple administration protocols. Study design: Experimental pharmacokinetic study. Methods: Three mares (Group 1) were administered a single i.m. dose of CCFA (6.6mg/kg bwt) and blood and endometrial biopsies were collected at selected intervals for 144h. Six additional mares (Groups 2 and 3) received CCFA at times 0, 4, 11 and 18 days, and were sampled at predetermined times for 25 or 49 days, respectively. Plasma and tissue samples were analysed by high-pressure liquid chromatography with tandem mass spectrometry for desfuroylceftiofur acetamide concentration, which is a direct measure of all ceftofur and ceftiofur metabolites in the sample. Results: A mean plasma desfuroylceftiofur acetamide concentration of 0.367 ± 0.0162μg/ml (mean ± s.e.) was detected at 96h following administration. Mean endometrial tissue concentration was 0.510 ± 0.0418μg/g at 96h and exceeded the MIC for S.zooepidemicus (0.25μg/ml) throughout the 144h monitoring period for Group 1. Mares in Groups 2 and 3, given multiple doses of CCFA, maintained plasma concentrations above the MIC for S.zooepidemicus for 25 days. Endometrial tissue levels remained above the MIC at most data collection points for 25 days. Conclusions: Ceftiofur crystalline free acid reaches appropriate endometrial tissue values to exceed the MIC of S.zooepidemicus, a common cause of bacterial endometritis. Therefore, CCFA should be effective in the treatment of equine bacterial endometritis caused by S.zooepidemicus and other susceptible bacterial pathogens in the mare.

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