Chemicals / Complex Chemical Agents/ Chemical:

Ampicillin (with special reference to Hedgehogs, Elephants, Bears, Lagomorphs, Ferrets, Great Apes and Cranes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
A bactericidal antibiotic in the "broad spectrum" aminopenicillin group. (B263)

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Names and Formulae
Type An aminopenicillin - a penicillin - a beta-lactam antibiotic. (B263) Antimicrobial.(W324)
Alternative Names
  • Aminobenzylpenicillin, AY-g108, BRL 1341. (B263)
  • "Wymox; Polycillin; Totacillin; Unasyn; Aminobenzylpenicillin; (2S,5R,6R)-6-[(R)-2-Amino-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-[(Aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid; 6-[D(-)-alpha-aminophenylacetamido]penicillanic acid; D(-)-alpha-aminobenzylpenicillin; Ampicillin A; Adobacillin; Alpen; Amblosin; Amfipen; Amipenix S; Ampi-Bol; Ampicin; Ampicina; Ampilar; Ampimed; Ampipenin; Ampi-Tablinen; Amplisom; Amplital; Ampy-Penyl; Austrapen; Binotal; Bonapicillin; Britacil; Copharcilin; Doktacillin; Grampenil; Guicitrina; Marisilan; Nuvapen; Pen-Bristol; Penbritin; Penbrock; Penicline; Penstabil; Pentrex; Pentrexyl; Ponecil; QI Damp; Rosampline; Synpenin; Tokiocillin; Totalciclina; Totapen; Ultrabion; Viccillin; Omnipen; 4-Thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid, 6-[(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-, [2S-[2alpha, 5alpha, 6beta(S*)]]-; Ampicillin Sulbactam; Ampicyn; D(-)-aplha-aminobenzylpenicillin; Amipenix; amino]-3,3,-dimethyl-7-oxo-4-thia-1-azabicyclo;("W324)
Chemical Formula C16H19N3O4S
Chemical Structure --
Molecular Weight 349.4038
Related Chemicals Amoxycillin, other aminopenicillins, other penicillins. 

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Physical Properties / Chemistry
Appearance
  • Ampicillin: white crystalline powder, practically odourless. (B263)

  • Ampicillin sodium: white to off-white hygroscopic crystalline powder. (B263)

  • Ampicillin trihydrate: white crystalline powder, practically odourless. (B263)

Melting point --
Boiling point --
Density --
Water solubility
  • Ampicillin: slightly soluble in water: 13 mg/ml at 20C. (B263)

  • Ampicillin sodium: very soluble in water. (B263)

  • Ampicillin trihydrate: slightly soluble in water: 6 mg/ml at 20C. (B263)

Other solubility --
Acid/Base Acid. (B201.1.w1)
  • Ampicillin: pH 5-7.5 following reconstitution with water. (B263)

  • Ampicillin sodium: at a concentration of 10 mg/ml, pH 8-10. (B263)

  • Ampicillin trihydrate: pH 5-7.5 following reconstitution with water. (B263)

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Pharmacology & General Information
Pharmacology
  • Generally bactericidal. Interfere with cell wall synthesis. (B201.1.w1)
  • Bind to various enzymes within the bacterial cytoplasmic membrane and inhibit mucopeptide synthesis in bacterial cell walls. This results in a defective cell wall and osmotically defective spheroplast. (B263)
  • More effective against actively growing bacteria. (B263)
  • Bactericidal only if active peptidoglycan synthesis is taking place, i.e. in actively growing bacteria. (B135.43.w43)
Storage / Stability
  • Ampicillin, ampicillin trihydrate: store capsules and powder for oral suspension at room temperature 15-30C. (B263)

  • Reconstituted oral suspension is stable for seven days at room temperature, 14 days if refrigerated (2-8C). (B263)

  • Ampicillin trihydrate for injection: stable for three months at room temperature, 12 months if refrigerated (2-8C). (B263)

  • Ampicillin sodium for injection: following reconstitution, use within one hour: relatively unstable once reconstituted. (B263

    • At lower concentrations longer storage times may be possible: at 30 mg/ml at 4C in water for injection or 0.9% sodium chloride, stable for up to 48 hours; at 20 mg/ml at 4C in water for injection or 0.9% sodium chloride, stable for up to 72 hours; at up to 30 mg/ml in lactated Ringer's solution at 4C stable for up to 24 hours. (B263)

    • Destruction of the drug may be hastened by the presence of dextrose. (B263)

Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Action
Appropriate Use
  • Against ampicillin-sensitive infections. (B201.1.w1)
Limitations
  • Poor against Klebsiella, some Proteus spp. and Pseudomonas spp. (B201.1.w1)
  • Susceptible to inactivation by beta-lactamase-producing bacteria such as Staphylococcus aureus. (B263); poor activity against beta-lactamase producing Staphylococcus aureus (B201.1.w1)
  • Broken down by beta-lactamases produced by staphylococci and by beta-lactamases produced by Gram-negative organisms such as Escherichia coli and Haemophilus spp. (acquired resistance). (B201.1.w1)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption
  • Less good absorption than amoxycillin following oral administration (in non-ruminants). (B201.1.w1, B263)
  • Better absorption when there is no food in the stomach. (B201.1.w1, B263)
  • In humans and monogastric animals following oral administration, approximately 30-55% absorbed. (B263).
  • Following parenteral (intramuscular or subcutaneous) administration, ampicillin trihydrate will reach serum levels of about 50% of those seen with a comparable dose of ampicillin sodium salt. (B263)
Distribution
  • Widely distributed to tissues including liver, lungs, muscle, bile, prostate (human), and to fluids (ascitic, pleural, synovial). (B263)
  • Very low levels are found in the aqueous humour of the eye. (B263)
  • Low levels are found in saliva, sweat and tears. (B263)
  • Crosses the placenta.. (B263)
  • Low levels in milk: in lactating dairy cattle, milk: plasma ration approximately 0.3:1. (B263)
  • During meningeal inflammation ampicillin crosses into the cerebrospinal fluid and may reach concentrations of 10-60% of serum levels. (B263)

Volume of distribution:

  • Dogs: 0.20 L/kg (B270); 0.3 L/kg (B263)
  • Cats: 0.167 L/kg. (B263)
  • Horses: 0.18 L/kg (B270)
  • Cattle: 0.16-0.5 L/kg (B263)
  • Sheep: 6.39 L/kg (B270);
  • Goats: 7.15 L/kg (B270);
  • Human: 0.3 L/kg. (B263);
Plasma Protein binding / Storage
  • About 205 plasma protein-bound, mainly to albumin. (B263)
Elimination Route
  • Excreted in urine. (B201.1.w1)
    • Mainly renal excretion by tubular secretion, also glomerular filtration. (B263)
    • Some of the drug is hydrolysed to inactive penicilloic acids prior to excretion in urine. (B263)
  • Excreted in bile. (B201.1.w1)
Elimination half-life / Clearance Rate Elimination half life:
  • Dogs, cats: 45-80 minutes. (B263)
  • Pigs: 60 minutes. (B263)
Drug Interactions
  • Use concurrent with aminoglycosides or cephalosporins may produce a synergistic effect against some bacteria. (B263)
  • Not recommended in combination with bacteriostatic antibiotics as penicillins are more effective against actively growing bacteri. (B263)
  • Low concentrations of ampicillin used in combination with rifampin may give an additive or synergistic effect; however high ampicillin concentrations may result in antagonism. (B263)
  • Concurrent use of probenecid gives a longer ampicillin serum half-life and higher serum level, due to blockage of tubular secretion of the penicillin. (B263)
  • Reported to be physically compatible with: heparin sodium, chloramphenicol sodium succinate, procaine hydrochloride, verapamil hydrochloride. (B263)
  • Reported to be physically incompatible with: amikacin sulphate, chlorpromazine hydrochloride, dopamine hydrochloride, erythromycin lactobionate, gentamicin hydrochloride, hydralazine hydrochloride, hydrocorticone sodium succinate, kanamycin sulphate, lincomycin hydrochloride, oxytetracycline hydrochloride, polymixin B sulphate, prochlorperazine edisylate, sodium bicarbonate, tetracycline hydrochloride. (B263)
  • Physical compatibility depends on factors such as concentration, temperature, pH and diluents. (B263)

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Administration
Formulations available
  • Depot preparations with the drug incorporated into an oily vehicle and containing aluminium monostearate are available. Such formulations allow prolonged action from a single injection. (B201.1.w1)
Doses / Administration Routes / Frequencies

Use of Drugs (Medication):

  • Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
  • Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
  • Consideration should be given to relevant legislation regarding the use of drugs.
  • In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).

General comments:

  • Dosing regimen should maintain the tissue concentration above the MIC for as long as possible during the inter-dosing interval. (B201.1.w1)
  • Dose required may vary with the size of the animal: in general the dosage per unit body weight increases as the size of the animal decreases. (B201.1.w1)
  • Dose required may vary with factors such as intercurrent disease and severity of infection. (B201.1.w1)
  • In general administration should continue with acute infections for two to three days after clinical cure and with chronic infections for one to two weeks after clinical cure; longer treatment may be required with some conditions. (B201.1.w1)
  • If giving orally, give on an empty stomach and at least an hour before feeding. (B201.1.w1)

Erinaceus europaeus - West European Hedgehog:

  • 10 mg/kg intramuscularly, twice daily. (B22.27.w3, B267, D107)
  • 20 mg/kg oral or subcutaneously. Broad spectrum bactericidal antibacterial. (B284.6.w6)

Atelerix albiventris - Four-toed hedgehog:

"Hedgehog" (species not distinguished between Atelerix albiventris - Four-toed hedgehog or Erinaceus europaeus - West European Hedgehog):
  • 10.0 mg/kg intramuscularly or orally, every 12 hours. (B150.w1)
  • 10 mg/kg intramuscularly every 12 hours. (B267)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 10 - 25 mg/kg or intramuscularly every 24 hours for 5 - 7 days. (B601.15.w15)
    • Do NOT give orally. (B601.15.w15)
  • Do not use in rabbits. (B546)

Elephants:

Elephas maximus - Asian Elephant

  • 25 g intramuscularly once daily for ten days was given to a 40-year-old, 3,300 kg female elephant with a nail infection. (J2.28.w2, P9.1.w7)

Loxodonta africana - African Elephant

  • 10 g intramuscularly daily was used in a juvenile elephant with salmonellosis [Salmonellosis]. (J4.185.w1)
  • 6.8 g intramuscularly daily for seven days and 6 g orally for three days was used in an elephant with salmonellosis. (P1.1985.w3)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w5):

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 g /ml), but is not likely to be effective against Salmonella spp. (MIC = 50 g /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 g /ml. Mean peak serum ampicillin concentration (0.86 g /ml) was reached 90 min after administration of the drug. The mean area under the concentration-time curve (AUC) was 208.6 106.4 g 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.

Bears:

  • In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)
  • Ampicillin was given orally in treatment of a Ursus maritimus - Polar bear at Chester Zoo, UK with unilateral submaxillary swelling during an outbreak of anthrax; the bear survived. (J3.92.w3)

Dogs:

  • 10-20 mg/kg twice daily on an empty stomach, or 7.5 mg/kg once daily by subcutaneous or intramuscular injection, or 15 mg/kg by depot subcutaneous injection, repeated after two days. (B373.1.w1)

Ferrets - Mustela putorius furo - Ferret:

  • 5.0 - 30 mg/kg subcutaneously, intramuscularly or orally, twice daily. "Broad spectrum" (B626.App.w22)
  • 5.0 - 30 mg/kg intravenously, intramuscularly or subcutaneously every 8 - 12 hours. (B602.41.w41, B631.21.w21)
  • 5 - 10 mg/kg subcutaneously, intramuscularly or intravenously twice daily. (J213.3.w1)

Great Apes

  • Adult Pan troglodytes - Chimpanzee: 20 mg/kg intravenously, intramuscularly or orally three times daily. (W768.Jun2012.w1)
  • Primates 50 mg/kg subcutaneously or intravenously three times daily.  (D425.3.15.w3o)

Cranes

  • 100 mg/kg intramuscularly twice daily. (B115.8.w4)
  • 20 mg/kg every 12 hours. (B12.56.w14)
  • 20 (up to 100) mg/kg intramuscularly every 12 hours. (B336.20.w20)
  • Broad spectrum, used against both Gram-positive and Gram-negative bacteria, including some pathogenic enteric organisms. (B12.56.w14, B115.8.w4)
Monitoring parameters
  • Monitor for efficacy. (B263)

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Withdrawal period / Withholding time
Notes Before the use of any pharmaceutical product in food-producing animals the label instructions for the product should be consulted regarding withdrawal requirements.
  • Varies with species and with preparation used. (B201.1.w1)
  • The withdrawal period specified by the manufacturer for a particular product in a particular species, as indicated in the appropriate Data Sheet for that product used in that country, must be consulted.
  • Should not be used in birds producing eggs for human consumption. (B201.1.w1)
  • Not for use in sheep producing milk for human consumption. (B201.1.w1)
  • In cattle milk withholding time may be e.g. one to seven days depending on the formulation. (B201.1.w1)
  • For slaughter may be as long as 28 days in cattle and pigs. (B201.1.w1)

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in patients with a history of sensitivity to penicillins. (B263)
  • Must be used with caution in patients with documented hypersensitivity to other beta-lactam antibiotics such as cephalosporins. In humans up to 15% of those hypersensitive to cephalosporins are also hypersensitive to penicillins. (B263)
  • In pregnancy use only if potential benefits outweigh the risks, as penicillins cross the placenta and safe use of penicillins during pregnancy has not been firmly established. (B263)
Adverse Effects / Side Effects / Warnings
  • Local irritation may occur at injection site occasionally. (B201.1.w1)
  • Diarrhoea. (B201.1.w1); may cause diarrhoea in hedgehogs. (D107)
  • Should not be administered to gerbils, guinea pigs, hamsters or rabbits. (B201.1.w1)
  • Should not be administered by intrathecal injection as this may result in seizures. (B201.1.w1)
  • Allergic reactions may occur. (B201.1.w1)
  • Hypersensitivity reactions:
    • Unrelated to dose. (B263)
    • May result in rash, fever, eosinophilia, neutropaenia, agranulocytosis, thrombocytopaenia, leucopaenia, anaemias, lymphadenopathy.
    • May cause full-blown anaphylaxis. (B263)
Operator Warnings
  • Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
  • "Accidental self-injection with oil-based formulations can cause severe pain and intense swelling, which may result in ischaemic necrosis and loss of a digit. Prompt medical attention is essential." (B201.1.w1)
  • As will all penicillins, may cause hypersensitivity (allergy) following self injection, inhalation, ingestion or skin contact. Should not be handled by operators with known hypersensitivity. Clinical signs of allergic reaction may include: skin rash, swelling of face, lips or eyes, difficulty in breathing. In the event of a reaction seek medical advice. (B201.1.w1)
Overdose / Acute Toxicity --

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources  
Biological Use  
Recommended Daily Allowance / Recommended level in food  
Stability in food (Storage time)  
Interactions  

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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