
Elephant Formulary
© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
www.elephantcare.org
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Ampicillin
Elephant specific information, if available, is in blue.
For general information on the penicillins, including adverse effects, contraindications, overdosage, drug interactions and monitoring parameters, refer to the monograph: Penicillins, General Information.
Chemistry – A semi-synthetic aminopenicillin, ampicillin anhydrous and trihydrate occur as practically odorless, white, crystalline powders that are slightly soluble in water. At usual temperatures (<42°C), ampicillin anhydrous is more soluble in water than is the trihydrate (13 mg/ml vs. 6 mg/ml at 20°C). Ampicillin anhydrous or trihydrate oral suspensions have a pH of 5-7.5 after reconstitution with water.
Ampicillin sodium occurs as an odorless or practically odorless, white to off-white, crystalline hygroscopic powder. It is very soluble in water or other aqueous solutions. After reconstitution, ampicillin sodium has a pH of 8-10 at a concentration of 10 mg/ml. Commercially available ampicillin sodium for injection has approximately 3 mEq of sodium per gram of ampicillin.
Potency of the ampicillin salts are expressed in terms of ampicillin anhydrous. Ampicillin may also be known as aminobenzylpenicillin , AY-6108, or BRL 1341.
Storage/Stability/Compatibility – Ampicillin anhydrous or trihydrate capsules and powder for oral suspension should be stored at room temperature (15-30°C). After reconstitution, the oral suspension is stable for 14 days if refrigerated (2-8°C) and is stable for 7 days when kept at room temperature.
Ampicillin trihydrate for injection (Polyflex® ) is stable for 12 months if refrigerated (2-8°C) and is stable for 3 months when kept at room temperature.
Ampicillin sodium for injection is relatively unstable after reconstitution and should generally be used within 1 hour of reconstitution. As the concentration of the drug in solution increases, the stability of the drug decreases. Dextrose may also speed the destruction of the drug by acting as a catalyst in the hydrolysis of ampicillin.
While most sources recommend using solutions of ampicillin sodium immediately, studies have demonstrated that at concentrations of 30 mg/ml, ampicillin sodium solutions are stable in sterile water for injection or 0.9% sodium chloride for up to 48 hours (72 hours if concentrations are 20 mg/ml or less) if kept at 4°C. Solutions with a concentration of 30 mg/ml or less have also been shown to be stable for up to 24 hours in solutions of lactated Ringer’s solution if kept at 4°C. Solutions of 20 mg/ml or less are reportedly stable for up to 4 hours in D5W if refrigerated.
Ampicillin sodium is reportedly compatible with the following additives (see the above paragraph for more information): heparin sodium, chloramphenicol sodium succinate, procaine HCl and verapamil HCl.
Ampicillin sodium is reportedly incompatible with the following additives: amikacin sulfate, chlorpromazine HCl, dopamine HCl, erythromycin lactobionate, gentamicin HCl, hydralazine HCl, hydrocortisone sodium succinate, kanamycin sulfate, lincomycin HCl, oxytetracycline HCl, polymyxin B sulfate, prochlorperazine edisylate, sodium bicarbonate and tetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology – Ampicillin and the other aminopenicillins have increased activity against many strains of gram negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella and Haemophilus. Like the natural penicillins they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staph aureus). Although not as active as the natural penicillins, they do have activity against many anaerobic bacteria, including Clostridial organisms. Organisms that are generally not susceptible include Pseudomonas aeruginosa, Serratia, Indole-positive Proteus (Proteus mirabilis is susceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses.
Uses/Indications – In dogs and cats, ampicillin is not as well absorbed after oral administration as is amoxicillin and its oral use has largely been supplanted by amoxicillin. It is used commonly in parenteral dosage forms when an aminopenicillin is indicated in all species.
Pharmacokinetics (specific) – Ampicillin anhydrous and trihydrate is relatively stable in the presence of gastric acid. After oral administration, it is about 30-55% absorbed in humans (empty stomach) and animals (monogastric). Food will decrease the rate and extent of oral absorption.
When administered parenterally (IM, SQ) the trihydrate salt will achieve serum levels of approximately 1/2 of those of a comparable dose of the sodium salt. The trihydrate parenteral dosage form should not be used where higher MIC’s are required for treating systemic infections.
After absorption the volume of distribution for ampicillin is approximately 0.3 L/kg in humans and dogs, and 0.167 L/kg in cats. The drug is widely distributed to many tissues, including liver, lungs, prostate (human), muscle, bile, and ascitic, pleural and synovial fluids. Ampicillin will cross into the CSF when meninges are inflamed in concentrations that may range from 10-60% of those found in serum. Very low levels of the drug are found in the aqueous humor and low levels are found in tears, sweat and saliva. Ampicillin crosses the placenta, but is thought to be relatively safe to use during pregnancy. Ampicillin is approximately 20% bound to plasma proteins, primarily albumin. Milk levels of ampicillin are considered to be low.
Ampicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, but some of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in the urine. Elimination half-lives of ampicillin have been reported as 45-80 minutes in dogs and cats, and 60 minutes in swine.
Doses –
Horses:
For susceptible infections:
a) Ampicillin sodium: 10 – 50 mg/kg IV or IM tid
Ampicillin trihydrate: 5 – 20 mg/kg IM bid (Robinson 1987)
b) Ampicillin sodium: 11 – 15 mg/IM or IV tid–qid (Beech 1987a)
c) Foals: Ampicillin sodium 20 mg/kg IV q6-8h (dose extrapolated from adult horses; use longer dosage interval in premature foals or those less than 7 days of age) (Caprile and Short 1987)
d) Ampicillin trihydrate: 11 mg/kg IM q6h
Ampicillin sodium: 22 mg/kg IM q12h (Upson 1988)
e) Ampicillin sodium 22 mg/kg IM q6-12h or 25 – 100 mg/kg IV q6h.
Ampicillin trihydrate: 11 – 22 mg/kg IM q12h (Brumbaugh 1987)
Elephants:
a) 8 mg/kg PO BID-TID for susceptible staphylcoccal and streptococcal pathogens. This dose may be effective against sensitive strains of Pasteurella multocida (MIC = 0.05 µg/ml), but is not likely to be effective against Salmonella spp. (MIC = .02 –2.5 µg/ml) or E.coli (MIC = 5.0 µg/ml).
Elephant References:
a) Rosin,E., Schultz-Darken,N., Perry,B., and Teare,J.A. 1993. Pharmacokinetics of ampicillin administered orally in Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 24:(4):515-518 Abstract:The purpose of this study was to determine the pharmacokinetics of ampicillin in Asian elephants (Elephas maximus) and to relate this information to the in vitro activity of ampicillin against two pathogens isolated from one elephant. A single oral dose of ampicillin trihydrate (8 mg/kg) was given to three elephants; body weights were estimated. Capsules containing the drug were hidden in oranges that were offered to the elephants, and ingestion was complete. The ampicillin minimum inhibitory concentration (MIC) for a streptococcal and staphylococcal elephant isolate was 0.06 µg /ml. Mean peak serum ampicillin concentration (0.86 µg /ml) was reached 90 min after administration of the drug. The mean area under the concentration-time curve (AUC) was 208.6 ± 106.4 µg x min/ml. The mean terminal half-life was 53.7 ± 8.9 min. Ampicillin concentrations in serum remained above MIC for longer than 8 hr.
Client Information – Unless otherwise instructed by the veterinarian, this drug should be given orally on an empty stomach, at least 1 hour before feeding or 2 hours after. Keep oral suspension in the refrigerator and discard any unused suspension after 14 days. If stored at room temperature, discard unused suspension after 7 days.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Veterinary-Approved Products:
Ampicillin Trihydrate Injection Powder for Suspension 10 g & 25 g (of ampicillin) vials.
Polyflex ® (Fort Dodge); (Rx) Approved for use in dogs, cats, and cattle. Withdrawal times (cattle; do not treat for more than 7 days): Milk = 48 hours; Slaughter = 6 days.
Ampicillin Sodium for Injection 1 gram & 3 gram vials (of ampicillin)
Amp-Equine® (Pfizer); (Rx) Approved for use in horses not intended for food.
Human-Approved Products:
Ampicillin Sodium Powder for Injection Vials 125 mg, 250 mg, 500 mg, 1 g, 2 g, 10 g; 500 mg, 1 g, and 2 gram piggyback units; Omnipen-N® (Wyeth-Ayerst) (Rx);Polycillin-N® (Apothecon) (Rx);Totacillin-N® (SK-Beecham) (Rx); generic (Rx)
Ampicillin Capsules (as either trihydrate or anhydrous) 250 mg, 500 mg; Many tradenames and generics; (Rx)
Ampicillin (as the trihydrate) Powder for Oral Suspension 25 mg/ml, 50 mg/ ml, 100 mg/ml in 20 ml, 80 ml, 100 ml, 150 ml, and 200 ml bottles; Many tradenames; (Rx)
Also available in fixed dose combinations with:
Probenecid: Powder for Oral Suspension: 3.5 g ampicillin (as trihydrate) & 1g probenecid/probenecid (oral): Polycillin-PRB® (Apothecon); Probampacin®, generic (Rx)
Sulbactam Sodium (injection): 1.5 g (1 g ampicillin sodium/.05 g sulbactam sodium) & 3 g (2 g ampicillin sodium/1 g sulbactam sodium);Unasyn® (Roerig) (Rx)