Captive elephants are prone to infections of the feet, lungs and skin, as evidenced by clinical and necropsy reports.3 Antimicrobials are commonly used to treat these infections with or without culture and sensitivity information. Often, treatment regimens are established with no pharmacokinetic data on the agents being used in these species. Many times, antimicrobial dosage regimens are extrapolated from equine doses or are allometrically scaled from other domestic species dosage regimens. There are only a few antimicrobials that have been studied for pharmacokinetic information in the elephant. These include trimethoprim-sulfadiazine, oxytetracycline, amikacin, amoxicillin, penicillin, and ampicillin.1,2,5,7,8 When treating animals without the benefit of pharmacokinetic information, there is risk of either overdosing or underdosing the medication to the animal resulting in adverse effects or ineffective dosing and the possibility of developing antimicrobial-resistant infections. More treatment options are needed that are based on scientific information in order to treat these appropriately.
A pharmacokinetic study using ceftiofur sodium (Naxcel, Pharmacia & Upjohn Company, Kalamazoo, MI, USA) was performed in our captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Health status was determined by physical condition, complete blood counts, and serum chemistry parameters.
Elephants were randomly assigned to either an intravenous (IV) or an intramuscular (IM) administration group for the first administration. At the end of this phase, the animals were not used again for minimum of 3 wk to ensure that the ceftiofur had cleared their system. Then, the groups were switched so that the group receiving the IV injections on the first set of trials received the IM injections the second time around and vice versa. The dosage of ceftiofur administered by either route was 1.1 mg/kg based on the recommended dosage ranges for cattle and horses.6
Blood samples were collected just prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48, and 72 h post-administration. Samples were collected in lithium heparin tubes, centrifuged within 10 min after collection, the plasma separated into cryovials and these aliquots frozen at -80°C until assayed. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometry assay.
Analysis showed a steady decline in plasma levels for both IV and IM administrations through the first 12 h. The IV dosing samples showed further decline through 24 h. Levels at 48 and 72 h were below detectible limits for this assay.
The study overall shows a similar pattern in decline of plasma levels between IM and IV administration of ceftiofur sodium in these elephants. Plasma concentrations for the IM samples were lower than expected. This likely could be adjusted by administering ceftiofur at a higher dosage rate of 2.2 mg/kg. This would result in an extremely large injection volume and necessitate increasing the number of injection sites. Efficacy of this drug at this dose is also dependent on the MIC of the target organism.
Results indicate that ceftiofur used at 1.1 mg/kg IM could be useful in elephants when given 2–3 times per day depending upon the type and location of infection.
The authors express their appreciation to the elephant staff and veterinary department at Busch Gardens, Tampa for their assistance with animal handling and sample collection, respectively.
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