Disposition of Ceftiofur Sodium in Swine following Intramuscular Treatment

Gilbertson, Terry J.; Roof, Ryan D.; Nappier, John L.; Zaya, Matthew J.; Robins, Russel H.; Stuart, Dorothy J; Krzeminski, Leo F.; Jaglan, P. S.

doi:10.1021/jf00049a041

Cited by 23 publications

(33 citation statements)

References 3 publications

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“…After DFC is liberated, it rapidly binds primarily to tissue proteins (>56%). These results are in agreement with previous observations in vivo (Beconi‐Barker et al ., 1995; Gilbertson et al ., 1995) where over 65% of the 14 C‐activity was associated with tissue proteins. The nature of the binding of DFC to proteins is being characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Desfuroylceftiofur‐cysteine disulfide (DFC‐cysteine), desfuroylceftiofur‐glutathione disulfide (DFC‐glutathione), and 3,3′‐desfuroylceftiofur‐disulfide (DFC‐dimer) were synthesized by C.L. Gatchell at Pharmacia and Upjohn Inc. following previously described techniques (Gilbertson et al ., 1995). Desfuroylceftiofur (DFC), was synthesized by S.C. Olson at Pharmacia and Upjohn Inc. as follows: Fifty‐four (54.0) grams of Ceftiofur hydrochloride standard, (Issue E, Pharmacia and Upjohn, Inc. control reference standard), 0.776 mL of 14 C‐ceftiofur sodium solution (specific activity 0.29 mCi/mL, Dupont NEN Products, Boston, MA, 94.5% pure), and 1 g dithioerythritol (Aldrich Chemical Company, Milawaukee, WI) were dissolved in 50 mL of 0.1 m borate buffer (38 g sodium borate, 7.9 g KCl, 2 L H 2 O, pH 9).…”

Section: Methodsmentioning

confidence: 99%

“…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%

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In vitro metabolism of ceftiofur in bovine tissues

Olson

Beconi-Barker

Smith

et al. 1998

Vet Pharm & Therapeutics

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vitro metabolism of ceftiofur in bovine tissues

Olson

Beconi-Barker

Smith

et al. 1998

Vet Pharm & Therapeutics

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“…This MRL, along with those established for other edible tissues, corresponds to an intake of approximately 87% of the ADI for a standard diet [3]. CF metabolism has been described in rats [4], dairy cattle [5], and swine [6]. The thioester bond in this compound is rapidly cleaved to give desfuroylceftiofur, which is further metabolized to a disulfide dimer and various desfuroylceftiofur-protein and amino acid conjugates.…”

Section: Introductionmentioning

confidence: 76%

A simple method for electroanalytical determination of ceftiofur in UHT milk samples using square-wave voltammetry technique

et al. 2010

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A simple electroanalytical method was developed to determine the antibiotic ceftiofur (CF) in milk. The method is based on the adsorptive accumulation of the drug on a hanging mercury-drop electrode (HMDE) and the accompanying initiation of a negative square wave, which yielded well-defined cathodic peaks at -0.60 V (1C) and -0.91 V (2C) vs. Ag/AgCl. Calibration graphs were constructed and statistical parameters were evaluated. At pH 2.5, the square-wave voltammetry method revealed linearity from 52.4 to 524 ng mL -1 (r = 0.997), which is in accordance with the tolerance level of 100 ng mL -1 for CF as a residue in bovine milk established by the Food and Drug Administration (FDA) and the European Union. The limits of detection and quantification were 1.86 and 6.20 ng mL -1 , respectively. The method was tested to determine CF in spiked milk samples using HPLC as reference method.

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“…Reported metabolites include desfuroylceftiofur (DFC), desfuroylceftiofur cysteine disulfide (DCCD), protein bound DFC and desfuroylceftiofur thiolacton (Jaglan et al 1989(Jaglan et al , 1992Gilbertson et al 1995;Berendsen et al 2009). Although no maximum residue limit (MRL) has been established for poultry muscle, it is important to realise that ceftiofur MRLs for other species are defined as the sum of all residues retaining the -lactam structure, expressed as DFC (EU/37/2010).…”

Section: Introductionmentioning

confidence: 99%