© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
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Elephant specific information, if available, is in blue.
For general information on the cephalosporins including adverse effects, contraindications, overdosage, drug interactions, and monitoring parameters, refer to the monograph: Cephalosporins, General Information.
Chemistry – Ceftiofur sodium and HCl are semisynthetic 3rd generation cephalosporins.
Storage/Stability/Compatibility – Unreconstituted ceftiofur sodium powder for reconstitution should be stored in the refrigerator (2°-8°C). Protect from light. Color of the cake may vary from off-white to tan, but this does not affect potency. After reconstitution with bacteriostatic water for injection or sterile water for injection, the solution is stable for up to 7 days when refrigerated and for 12 hours at room temperature (15-30°C). According to the manufacturer, if a precipitate should form while being stored refrigerated during this time, the product may be used if it goes back into solution after warming. If not, contact the manufacturer. Frozen reconstituted solutions are stable for up to 8 weeks. Thawing may be done at room temperature or by swirling the vial under running warm or hot water.
The HCl product should be stored at controlled room temperature (20°-25°C; 68°-77°F) and protected from freezing. It should be shaken well before use.
Pharmacology/Spectrum of Activity – Ceftiofur inhibits cell wall synthesis (at stage three) of susceptible multiplying bacteria. Ceftiofur exhibits a spectrum of activity similar to that of cefotaxime. It has a broad range of in vitro activity against a variety of pathogens, including many species of Pasturella, Streptococcus, Staphylococcus, Salmonella, and E.coli.
Uses/Indications – Ceftiofur sodium/HCl is indicated for treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Pasturella hemolytica, Pasturella multocida and Haemophilus somnus in lactating or non-lactating cattle and ceftiofur sodium is indicated in horses for respiratory disease associated with Strep zooepidimicus:. Ceftiofur HCl is also approved for foot rot in cattle.
Ceftiofur could potentially be of usefulness in small animal infections as well, but little published data is available to recommend its use.
Pharmacokinetics (specific) – In cattle, ceftiofur sodium and HCl have practically equivalent pharmacokinetic parameters. Peak levels of ceftiofur are slightly higher after IM injection of Naxcel®, but areas under the curve are practically equal as well as elimination half-lives (approx. 9-12 hours).
For labeled indications:
a) Naxcel®: 1.1 – 2.2 mg/kg IM once daily for 3 treatments; may give additional doses on 4th and 5th day if response is not satisfactory. Reconstitute 1 g vial with 20 ml and the 4 g vial with 80 ml of either Bacteriostatic Water for Injection or Sterile Water for Injection. (Package Insert; Naxcel®—Upjohn)
b) Excenel®: 1.1 – 2.2 mg/kg IM or SQ once daily for 3 treatments; may give additional doses on 4th and 5th day if response is not satisfactory. For BRD only: May inject 2.2 mg/kg IM or SQ every other day (days 1 and 3; 48 hour interval). Do not inject more than 15 ml pe IM injection site. (Package Insert; Excenel ®—Pharmacia/Upjohn)
For respiratory disease associated with Strep zooepidimicus::
a) Naxcel®: 2.2 – 4.4 mg/kg (2 – 4 ml reconstituted sterile solution per 100 lb. of body weight) with a maximum of 10 ml administered per injection site. Repeat treatment at 24 hour intervals, continued for 48 hours after symptoms have disappeared. Do not exceed 10 days of treatment. (Package Insert; Naxcel®—Upjohn)
a) 2.2 – 4.4 mg/kg (Houck, 1986)
b) 1.1 mg/kg IM (Schmidt, 1986)
c) Naxcel can be reconstituted with less diluent than the package recommendations (25 to 35 ml vs 80 ml) and injections are well-tolerated (Mikota, 2003).
d) 1.1 mg/kg IM BID or TID or 1.1 mg/kg IV SID depending on the MIC of the pathogen (Dumonceaux, 2005).
e) e) 6.6 mg/kg SQ q 7-10 days: Ceftiofur crystalline-free acid (CCFA) long-acting (Brand name Excede, 200 mg/ml, Pfizer Inc. New York, New York). (pharmacokinetic study)
f) See also Cephalosporins (General Information)
a) Houck, R: Senior Veterinarian, Ringling Brothers and Barnum and Bailey Circus, 8607 Westwood Center Drive, Vienna, Virginia, 22182, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders,
Philadelphia, PA,USA p. 538
b) Schmidt, M.J: Senior Research Veterinarian, Washington Park Zoo, Portland, Oregon, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p. 538
c) Author’s (Mikota) experience.
Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.
d) Dumonceaux, G, Isaza, R. Koch, D.E., and Hunter, R.P. 2005. Pharmacokinetics and i.m. bioavailability of ceftiofur in Asian elephants (Elephas maximus). J Vet Pharmacol Ther. 28(5):441-6.
e) Adkesson MJ, Junge RE, Allender MC, Martin-Jimenez T: Pharmacokinetics of a long-acting ceftiofur crystalline-free acid formulation in Asian elephants (Elephas maximus). Am J Vet Res 2012, 73(10):1512-1518.
Objective—To determine the pharmacokinetics of a long-acting formulation of ceftiofur,
ceftiofur crystalline-free acid (CCFA), following SC injection to Asian elephants (Elephas
Animals—11 adult Asian elephants.
Procedures—Each elephant received CCFA (6.6 mg/kg, SC) in the area caudoventral to the base of an ear. Blood samples were collected from an ear vein immediately prior to and at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after CCFA administration.
Plasma concentrations of desfuroylceftiofur acetamide (the acetamide derivative of ceftiofur) were measured via ultrahigh-pressure liquid chromatography–tandem mass spectrometry. Data were analyzed via a noncompartmental pharmacokinetics approach. Results—The mean ± SD maximum plasma concentration of desfuroylceftiofur acetamide was 1.36 ± 0.74 μg/mL and was detected at 47.18 ± 31.30 hours. The mean ± SD area under the curve from time 0 to infinity was 227.8 ± 55.8 μg•h/mL, and the mean residence time
from time 0 to infinity was 158.2 ± 90.2 hours. The terminal elimination half-life associated with the slope of the terminal phase had a harmonic mean ± pseudo-SD of 83.36 ± 30.01 hours. Conclusions and Clinical Relevance—Elephants tolerated CCFA at a dose of 6.6 mg/kg, SC, well. Dosing recommendations will depend on the mean inhibitory concentration of ceftiofur for each bacterial pathogen. Desfuroylceftiofur acetamide concentrations remained > 0.25 μg/mL for the entire 168-hour study period, which suggested CCFA would
provide clinically relevant antimicrobial activity against certain pathogens for 7 to 10 days.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Ceftiofur Sodium Powder for Injection 1 g, 4 g vials; Naxcel® (Pharmacia&Upjohn); (Rx) Approved for use in cattle and horses. No slaughter withdrawal or milk withholding time are required when administered as labeled.
Ceftiofur HCl Suspension for Injection 50 mg(of ceftiofur)/ml in 100 ml vials; Excenel® (Pharmacia&Upjohn); (Rx). Approved for use in cattle. Slaughter withdrawal=48 hours; no milk withholding time required when administered as labeled.
Human-Approved Products: None