[14C]Ceftiofur Sodium Absorption, Distribution, Metabolism, and Excretion in Sheep following Intramuscular Injections

Beconi-Barker, Maria G.; Davison, K. L.; Hornish, Rex E.; Arnold, Thomas; Craigmill, Arthur L.; Gilbertson, Terry J.; Smith, Evan; Vidmar, Thomas J.; Hoffman, Gregory A.; Gatchell, Cathy L.

doi:10.1021/jf00054a033

Cited by 20 publications

(24 citation statements)

References 7 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In pigs, fecal and urinary excretion of ceftiofur ranged from 81 to 95% of total administered when IM dose varied between 3.08 and 6.76 mg/kg body weight [52]. Ceftiofur was almost completely (92.5% in urine and 6.5% in feces) excreted by sheep administered with 5 IM doses at 2.2 mg/kg body weight [53]. These cephalosporin formulations are designed to be absorbed for distribution to target tissues.…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

et al. 2014

View full text Add to dashboard Cite

Cephapirin, a cephalosporin antibiotic, is used by the majority of dairy farms in the US. Fecal and urinary excretion of cephapirin could introduce this compound into the environment when manure is land applied as fertilizer, and may cause development of bacterial resistance to antibiotics critical for human health. The environmental loading of cephapirin by the livestock industry remains un-assessed, largely due to a lack of appropriate analytical methods. Therefore, this study aimed to develop and validate a cephapirin quantification method to capture the temporal pattern of cephapirin excretion in dairy cows following intramammary infusion. The method includes an extraction with phosphate buffer and methanol, solid-phase extraction (SPE) clean-up, and quantification using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The LOQ values of the developed method were 4.02 µg kg−1 and 0.96 µg L−1 for feces and urine, respectively. This robust method recovered >60% and >80% cephapirin from spiked blank fecal and urine samples, respectively, with acceptable intra- and inter-day variation (<10%). Using this method, we detected trace amounts (µg kg−1) of cephapirin in dairy cow feces, and cephapirin in urine was detected at very high concentrations (133 to 480 µg L−1). Cephapirin was primarily excreted via urine and its urinary excretion was influenced by day (P = 0.03). Peak excretion (2.69 mg) was on day 1 following intramammary infusion and decreased sharply thereafter (0.19, 0.19, 0.08, and 0.17 mg on day 2, 3, 4, and 5, respectively) reflecting a quadratic pattern of excretion (Quadratic: P = 0.03). The described method for quantification of cephapirin in bovine feces and urine is sensitive, accurate, and robust and allowed to monitor the pattern of cephapirin excretion in dairy cows. This data will help develop manure segregation and treatment methods to minimize the risk of antibiotic loading to the environment from dairy farms.

show abstract

Section: Resultsmentioning

confidence: 99%

Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These results could be related to the particular metabolism of this antibiotic (Hornish and Kotarski 2002). Unlike other cephalosporins, like cephalexin, that are excreted primarily in urine unmetabolized, ceftiofur is rapidly metabolized to desfuroylceftiofur (Beconi‐Barker et al . 1995; Hornish and Kotarski 2002).…”

Section: Resultsmentioning

confidence: 99%

“…1995; Hornish and Kotarski 2002). Although there are no studies about the depletion of ceftiofur from ewe milk, several authors indicated that the pharmacokinetics of this drug in sheep is similar to those seem in cattle (Beconi‐Barker et al . 1995; Craigmill et al .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Influence of cephalosporins on the coagulation time of yogurt made from ewes’ milk

Berruga

Novés

Molina

et al. 2008

Int J of Dairy Tech

View full text Add to dashboard Cite

Ceftiofur and cephalexin were independently added to ewes’ milk at three different concentrations 50, 100 and 150 µg/kg. Spiked milk was used to produce yogurt and the acidification of the yogurt during incubation was then studied. Ceftiofur showed significant delays in the pH decrease rate at all concentrations assayed, but no significant delays occurred with cephalexin. When these antibiotics were administered intramuscularly to lactating ewes, from which the milk was used to make yogurt immediately after the corresponding withdrawal periods, absence of residues and pH delays were not observed during the yogurt fermentation in the presence of any antibiotic.

show abstract

“…Traditionally, whole animal models have been used for characterization of the metabolism in the target species and in the species used for pathological and toxicological evaluations. Whole animal studies indicated that ceftiofur sodium (NAXCEL®/EXCENEL Sterile Powder) is rapidly metabolized to desfuroylceftiofur (DFC) and furoic acid in the target species and in the rat (Jaglan et al ., 1989; Jaglan et al ., 1992; Gilbertson et al ., 1995; Beconi‐Barker et al ., 1995). In these metabolism studies DFC, the microbiologically active metabolite of ceftiofur, was never detected free, but was always found conjugated to proteins (70–90%), and to cysteine (DFC‐cysteine) in tissues and in plasma.…”

Section: Introductionmentioning

confidence: 99%

In vitro metabolism of ceftiofur in bovine tissues

Olson

Beconi-Barker

Smith

et al. 1998

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the effects of the presence of cystine and glutathione in the media were evaluated using S-9 and microsomal tissue fractions. Conversion of ceftiofur to desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in kidney, followed by liver. It was not very active in muscle and lung. After DFC was liberated, it rapidly bound primarily to tissue proteins (> 56%), and was also conjugated to cysteine and glutathione. Production of DFC-cysteine by disulfide exchange of DFC with cystine and production of DFC-glutathione by conjugation of DFC to glutathione occurred in buffer if glutathione and cystine were present in the medium. These conjugations were also observed in incubations with tissue fractions, indicating that they were not inhibited by the tissues endogenous molecules. In addition, the metabolism of DFC-glutathione to DFC-cysteine was observed when tissue proteins were present. The metabolism of DFC-glutathione to DFC-cysteine was faster in kidney than in liver. Metabolites devoid of an intact beta-lactam ring were not observed in these in vitro studies.

show abstract

[14C]Ceftiofur Sodium Absorption, Distribution, Metabolism, and Excretion in Sheep following Intramuscular Injections

Cited by 20 publications

References 7 publications

Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

Development and Validation of a UPLC-MS/MS Method to Monitor Cephapirin Excretion in Dairy Cows following Intramammary Infusion

Influence of cephalosporins on the coagulation time of yogurt made from ewes’ milk

In vitro metabolism of ceftiofur in bovine tissues

Contact Info

Product

Resources

About