Ceftiofur Sodium: Absorption, Distribution, Metabolism, and Excretion in Target Animals and Its Determination by High-Performance Liquid Chromatography

Beconi-Barker, Maria G.; Roof, Ryan D.; Vidmar, Thomas J.; Hornish, Rex E.; Smith, Evan; Gatchell, Cathy L.; Gilbertson, Terry J.

doi:10.1021/bk-1996-0636.ch009

Cited by 7 publications

(15 citation statements)

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“…(under excretion pattern 1 or 2) [51]; metabolites reached the large intestine in Tδ = 6 hours post excretion. Volume of the large intestine was 20L in an adult cattle, and 5L in a 6-mos calf.…”

Section: Methodsmentioning

confidence: 99%

Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

et al. 2012

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Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter.

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Section: Methodsmentioning

confidence: 99%

Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

et al. 2012

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“…At assignment, each calf received a single dose of placebo or CCFA‐SS administered s.c. in the neck at 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg BW. The range of doses tested was based on pilot pharmacokinetic studies conducted using a validated method (Beconi‐Barker et al ., 1996) to determine plasma drug concentrations over time.…”

Section: Methodsmentioning

confidence: 99%

Dose determination and confirmation of a long‐acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

Hibbard¹,

Robb²,

Chester³

et al. 2002

Vet Pharm & Therapeutics

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The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil(R) 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1-8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4-8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4-5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4-5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time.

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“…The model equations are included in the Supplementary Materials. Based on the relatively short time post-treatment of the occurrence and the amounts of CE as a fraction of the injected ceftiofur in cattle feces [41], we assumed that CE transited with the liquid digesta phase. For this reason, the diet was not varied for the simulations.…”

Section: Model Structurementioning

confidence: 99%

Models of antimicrobial pressure on intestinal bacteria of the treated host populations

2017

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Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

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Ceftiofur Sodium: Absorption, Distribution, Metabolism, and Excretion in Target Animals and Its Determination by High-Performance Liquid Chromatography

Cited by 7 publications

References 0 publications

Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Dose determination and confirmation of a long‐acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease

Models of antimicrobial pressure on intestinal bacteria of the treated host populations

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