Chemicals / Complex Chemical Agents/ Chemical:

Penicillin G (with special reference to Hedgehogs, Elephants, Bears, Lagomorphs, Ferrets and Great Apes)

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, a natural penicillin. (B263)

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Names and Formulae
Type A natural penicillin, obtained from cultures of Penicillium crysogenum; a beta-lactam antibiotic. (B263)
Alternative Names Benzylpenicillin. (B263)

"Benzyl penicillinic acid sodium salt; penicillin g, sodium salt; 3,3-dimethyl-7-oxo-6-(2-phenyl-acetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, monosodium salt; american penicillin; benzylpenicillin sodium; crystapen; mycofarm; novocillin; pen-a-brasive; penicillin-g, monosodium salt; penilaryn; sodium benzylpenicillin g; sodium benzylpenicillinate; sodium penicillin; sodium penicillin ii; veticillin; nalpen g; Picibanil". (W324)

Chemical Formula C16H17N2NaO4S (W324)
Chemical Structure --
Molecular Weight 356.37107. (W324)
Related Chemicals Other penicillins; other beta-lactam antibiotics. (B263)

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Physical Properties / Chemistry
Appearance
  • Crystalline powder, white to slightly yellow. (W324)

  • Penicillin G potassium (benzylpenicillin potassium): colourless or white crystals, white crystalline powder. (B263);

  • Penicillin G sodium (benzylpenicillin sodium): colourless or white crystals, white to slightly yellow crystalline powder. (B263, W324)

  • Penicillin G procaine (procaine penicillin): white crystals or fine white crystalline powder. (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): (B263)

Melting point 209 - 212 C. (W324)
Boiling point  
Density 1.41. (W324)
Water solubility
  • 5-10 g/100 mL at 25 C. W324)

  • Penicillin G potassium (benzylpenicillin potassium): very soluble in water. (B263)

  • Penicillin G sodium (benzylpenicillin sodium): solubility about 25mg/ml water. (B263)

  • Penicillin G procaine (procaine penicillin): 4.0-4.5 mg/ml water. (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): 0.2-0.3 mg/ml water. (B263)

Other solubility
  • Penicillin G potassium (benzylpenicillin potassium): "sparingly soluble".(B263)

  • Penicillin G sodium (benzylpenicillin sodium): -- (B263)

  • Penicillin G procaine (procaine penicillin): 3.3 mg/ml alcohol. (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): 15 mg/ml alcohol. (B263)

Acid/Base
  • Penicillin G potassium (benzylpenicillin potassium): (Reconstituted powder for injection) pH 6.0-8.5(B263)

  • Penicillin G sodium (benzylpenicillin sodium): (reconstituted powder for injection) pH 6.0-7.5. (B263)

  • Penicillin G procaine (procaine penicillin): (suspension for injection, buffered with sodium citrate) pH 5.0-7.5. (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): (suspension for injection, buffered with sodium citrate) pH 5.0-7.5. (B263)

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Pharmacology & General Information
Pharmacology
  • Generally bactericidal against susceptible bacteria. (B263) Interferes 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)
Storage / Stability
  • Penicillin G potassium (benzylpenicillin potassium): (B263)

    • Oral powder / tablets: store at room temperature in tight container. Protect from excessive heat. Protect from moisture to prevent hydrolysis. (B263)

    • Reconstituted oral powder for solution: store refrigerated (2-8C) for up to 14 days. (B263)

    • Powder for injection: room temperature (15-30C). (B263)

    • Reconstituted powder for injection: store refrigerated for up to seven days or at room temperature for up to 24 hours. (B263)

  • Penicillin G sodium (benzylpenicillin sodium): (B263)

    • Powder for injection: room temperature (15-30C); protect from moisture to prevent hydrolysis. (B263)

    • Reconstituted powder for injection: store refrigerated for up to seven days or at room temperature for up to 24 hours. (B263)

  • Penicillin G procaine (procaine penicillin): (B263)

    • Store refrigerated at 2-8C; avoid freezing. (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): 

    • Store refrigerated at 2-8C. (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
Activity
  • Group A betahaemolytic streptococci, many Gram-positive anaerobic bacteria, spirochaetes, Gram-negative aerobic cocci, some Gram-negative aerobic bacilli. (B263) In vitro, active against most spirochaetes, gram positive aerobic cocci, gram negative aerobic cocci. Active against some aerobic and anaerobic Gram-positive bacilli such as Bacillus anthracis, Clostridium spp. (but not Clostridium difficile), Fusobacterium, Actinomyces. (B263)
Appropriate Use
  • For infections with bacteria susceptible to penicillin G. (B263)
Limitations
Notes --

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Pharmacokinetics and Drug Interactions
Absorption / Oral Absorption / Bioavailability
  • Potassium penicillin G. (B263)
    • Poor absorption due to rapid acid-catalysed hydrolysis. May be completely inactivated at pH <2. (B263)
    • Bioavailability about 15-30% on an empty stomach; reduced absorption rate and extent if given with food. (B263)
Distribution
  • Widely distributed, throughout the body except for the CSF (about 10% of serum concentrations, but may be higher if meninges are inflamed), joints and milk (milk to plasma ration about 0.2 in lactating dairy cattle). (B263)

Potassium penicillin G, sodium penicillin G: (B263)

  • Intramuscular injection gives high peak levels within about 20 minutes of injection. (B263)
  • In horses, longer action with intramuscular than intravenous injection. (B263)

Procaine penicillin G:

  • Following intramuscular injection, slow hydrolysis to penicillin G, giving lower peak levels than with potassium penicillin G or sodium penicillin G but a longer time of serum presence. (B263)

Benzathine penicillin G:

  • Following intramuscular injection, slow hydrolysis to penicillin G, giving a prolonged time of serum presence but much lower peak levels than with potassium penicillin G or sodium penicillin G; generally exceeds MIC only for very sensitive streptococci.. (B263)
Plasma Protein binding / Storage
  • Approximately 50% plasma protein bound in most species. (B263)
Elimination Route
  • Mainly renal, both glomerular filtration and tubular secretion, excreted unchanged. (B263)
Elimination half-life / Clearance Rate
  • Elimination half-life in most species one hour or less if renal function is normal. (B263)
Drug Interactions
  • Not recommended in combination with bacteriostatic antibiotics as penicillins are more effective against actively growing bacteria. (B263)
  • Concurrent use of probenecid may increase serum level and half-life of penicillin due to competitive blockage of tubular secretion. (B263)
  • Penicillins in combination with aminoglycosides or cephalosporins may have synergistic or additive activity against some bacteria.  (B263)

Physical incompatibilities reported (or conflicting data):

  • Penicillin G potassium (benzylpenicillin potassium): "amikacin sulfate, aminophylline, cephalothin sodium, chlorpromazine HCl, dopamine HCl, heparin sodium, hydroxyzine HCl, lincomycin HCl, metoclopramide HCl, oxytetracycline HCl, pentobarbital sodium, prochlorperazine mesylate, promazine HCl, promethazine HCl, sodium bicarbonate, tetracycline HCl and vitamin B complex with C." (B263)

  • Penicillin G sodium (benzylpenicillin sodium): "amphotericin B, bleomycin sulfate, cephalothin sodium, oxytetracycline HCl, potassium chloride, prochlorperazine mesylate, promethazine HCl and tetracycline HCl." (B263)

  • Penicillin G procaine (procaine penicillin): (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): (B263)

Physical compatibility reported:

  • Penicillin G potassium (benzylpenicillin potassium): "Commonly used intravenous fluids (some Dextran products are physically incompatible), ascorbic acid injection, calcium chloride/gluconate, cephapirin sodium, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, corticotropin, dimenhydrinate, diphenhydramine HCl, ephedrine sulfate, erythromycin gluceptate/lactobionate, hydrocorticone sodium succinate, kanamycin sulfate, lidocaine HCl, methicillin sodium, methylprednisolone sodium succinate, metronidazole with sodium bicarbonate, nitrofurantoin sodium, polymyxin B sulfate, potassium chloride, prednisolone sodium phosphate, procaine HCl, prochlorperazine edisylate, sodium iodide, sulfisoxazole diolamine and verapamil HCl." (B263)

  • Penicillin G sodium (benzylpenicillin sodium): "Dextran 40 10%, dextrose 5% (some degradation may occur if stored for 24 hours), sodium chloride 0.9% (some degradation may occur if stored for 24 hours), calcium chloride/gluconate, chloramphenicol sodium succinate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, diphenhydramin HCl, erythromycin lactobionate, gentamicin sulfate, hydrocortisone sodium succinate, kanamycin sulfate, methicillin sodium, nitrofurantoin sodium, polymyxin B sulfate, prednisolone sodium phosphate, procaine HCl, verapamil Hcl and vitamin B-complex with C." (B263)

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Administration
Formulations available
  • Penicillin G potassium (benzylpenicillin potassium): (B263)

  • Penicillin G sodium (benzylpenicillin sodium): (B263)

  • Penicillin G procaine (procaine penicillin): (B263)

  • Penicillin G Benzathine (Benzathine benzylpenicillin): (B263)

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).

For antibiotic cover in a single injection for wounds (e.g. in the field):

  • Procaine penicillin/benzathine penicillin, sufficient to give 22,000 IU/kg of the benzathine penicillin G to ensure an adequate repository effect giving antibiotic cover for 5-7 days, subcutaneously or into the large muscles of the hind legs, with a large bore (18 gauge) needle, at no more than 5 mL per injection site). (B345.4.w4)

Erinaceus europaeus - West European Hedgehog:

  • 40,000 IU/kg intramuscularly every 24 hours. (B22.27.w3, B267)

Atelerix albiventris - Four-toed hedgehog:

"Hedgehog" (species not distinguished between Atelerix albiventris - Four-toed hedgehog or Erinaceus europaeus - West European Hedgehog):
  • 40,000 IU/kg intramuscularly once daily. (B150.w1)

In Elephants:

  • 5000 to 20,000 IU/kg was given for treatment of anthrax. (B64.27.w4)
  • 16 million IU daily for an adult elephant for anthrax infection. (B214.3.7.w3)

Elephas maximus - Asian Elephant

  • 10,000,000 units daily for 5 days for a 25-year-old male showing respiratory signs and weakness (route of administration not specified). (J196.60.w1)
  • 100 cc intramuscularly once daily for five days was given to a 40-year-old 3,300 Kg female with a nail infection. (J2.28.w2, P9.1.w7)
  • Sixteen grams of gentamicin sulfate diluted in one liter of lactated Ringer's solution intravenously once daily and 42 x 10 benzathine and procaine penicillin intramuscularly once daily were administered for 10 days after a second surgery to amputate a toenail to a 40-year-old 3,300 kg female. For nail infection complicated with phalangeal osteomyelitis. (J2.28.w2, P9.1.w7)

Loxodonta africana - African Elephant

  • The following uses have been described:
  • 6,000,000 IU long-acting penicillin intramuscularly every other day perioperatively. (J4.189.w3)
  • Eighteen million USP Units intramuscularly perioperatively for a 17 year-old female. (J3.152.w2)
  • 8 x 107 IU in four liters of normal saline solution intravenously for an adult 3,600 kg elephant in a case of respiratory disease. (J4.189.w5)
  • 5670 IU/kg intramuscularly once daily as first choice broad spectrum antibiotic in a case of acute enteritis. (P30.1.w5)
  • An infected fistulous tract of the tusk in a six-year-old Loxodonta africana - African Elephant was flushed daily with 2 x 106 penicillin G potassium for ten days, based on culture of organisms from the tract (several antibiotics were used in succession, based on culture and sensitivity each time; this was the last antibiotic used, until culture was negative). (J4.189.w4)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w26):

Elephants:
a) Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 96 hours for Bacillus anthracis, Corynebacterium diphtherae, Streptococci spp, Staphylococci (non- penicillinase producing).

Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 2,273/kg q 48 h for Bacillus anthracis, Corynebacterium diphtherae, Streptococci spp, Staphylococci (non-penicillinase producing).

Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 36 h for Clostridia

Procaine penicillin G (150,000 IU/ml) in combination with benzathine penicillin (150,000 IU / ml): 4,545 IU/kg q 24 h for Pasteurella multocida (Schmidt, 1978).

Elephant References:
a) Schmidt,M.J. 1978. Penicillin and amoxicillin in elephants: A study comparing dose regimens administered with serum levels achieved in healthy elephants. Journal of Zoo Animal Medicine 9:(4):127-136 Abstract: Several dose regimens of an aqueous suspension of benzathine penicillin G combined with procaine penicillin G, and an aqueous suspension of amoxicillin were administered to five healthy adult female Asian elephants. Blood samples were drawn and serum levels of the drugs were measured after each dose was administered. Based upon serum levels, suggestions are made for therapeutic dose regimens for clinical use of both penicillin and amoxicillin in elephants, based on comparable data available for other large domestic animals.

In Bears:

  • In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)
  • As a preventative to minimise the risk that a debilitating abscess will form following darting, particularly with a powder-charged dart, procaine penicillin/benzathine penicillin (dosing to give 22,000 IU/kg of the benzathine penicillin G to ensure an adequate repository effect giving antibiotic cover for 5-7 days) , subcutaneously or into the large muscles of the hind legs, with a large bore (18 gauge) needle, at no more than 5 mL per injection site). (B345.4.w4)
  • As treatment for Dermatophilosis in Bears, long acting penicillin intramuscularly: 
    • In an adult bear, initially 30,000 units/kg (3 megaunits benzathine penicillin G, 1.5 megaunits procaine penicillin G, 1.5 megaunits potassium penicillin G, 45,000 to 60,000 units per kg twice weekly for eight weeks. Then increased to 45,000 units/kg (9 megaunits total), twice weekly for eight weeks. (J4.167.w2)
    • In an eighteen-month-old bear, initially 60,000 units/kg (6 megaunits), followed by 30,000 units/kg (3 megaunits) on subsequent treatments, intramuscularly twice weekly for eight weeks. (J4.167.w2)
  • For prevention of Navel Infection in Bears, intramuscular 75,000 units of benzathine penicillin G. (B64.26.w5)
  • Procaine penicillin G (2 x 106 ) units was given as part of initial treatment in a bear with a ruptured intervertebral disk. (J4.177.w3)
  • In bears undergoing Cholecystectomy in Bears, 1 000 000 IU penicillin G, suspended in 5 mL of sterile water, is infused into the abdominal cavity before the abdomen is closed. (V.w89)

In Dogs:

  • 1 mL/10 kg bodyweight by intramuscular injection, repeated after 3-4 days if required. (B373.1.w1)
    • 1 mL suspension contains 112.5 mg benzathine benzylpenicillin plus 150 mg/mL procaine benzylpenicillin. (B373.1.w1)
Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:
  • 40 mg/kg subcutaneously once every seven days for three doses for the treatment of Treponematosis in Lagomorphs. (B546)
  • 40 mg/kg subcutaneously every 24 hours. (B546)
  • 40,000 - 60,000 IU/kg intramuscularly every 12 hours for five to seven days. (B548.w8)
  • Benzathine penicillin G 42,000 - 60,000 IU/kg intramuscularly every 48 hours. (B548.w8)
  • Benzathine penicillin G 42,000 - 84,000 IU/kg subcutaneously every seven days for three weeks. For the treatment of Treponematosis in Lagomorphs. (B548.w8)
  • Procaine penicillin G 40,000 IU/kg intramuscularly every 24 hours for five to seven days. For the treatment of Treponematosis in Lagomorphs. (B548.w8)
  • Procaine penicillin G 42,000 - 84,000 IU/kg subcutaneously or intramuscularly every 24 hours. (B548.w8)
  • Procaine penicillin G 60,000 IU/kg intramuscularly every eight hours. (B548.w8)
  • 40,000 IU/kg (40 mg/kg) subcutaneously once daily. (B600.4.w4)
    • Notes: Active against Pasteurella. Risk of antibiotic-associated diarrhoea if given orally. (B600.4.w4)
  • 40,000 IU/kg (40 mg/kg) of procaine penicillin subcutaneously once daily for five days. In the treatment of Treponematosis in Lagomorphs. (B600.4.w4)
  • 20 mg/kg procaine penicillin plus 15 mg/kg benzathine penicillin subcutaneously weekly (three injections) Treatment of choice for Treponematosis in Lagomorphs, where available. (B600.4.w4)
  • 40,000 IU/kg intramuscularly daily for seven days. In the treatment of Treponematosis in Lagomorphs. (B601.15.w15)
  • 40,000 - 60,0000 IU/kg subcutaneously every 48 hours "use with caution". (B602.41.w41)
  • Procaine +/- benzocaine penicillin 40 mg/kg (40,000 U/kg) subcutaneously. (B603.5.w5)
  • 80 mg/kg procaine penicillin once a week for three weeks for the treatment of Treponematosis in Lagomorphs. (B603.5.w5)

Ferrets - Mustela putorius furo - Ferret:

  • 40,000 IU/kg sodium/potassium penicillin G (benzylpenicillin potassium / benzylpenicillin sodium) intramuscularly once daily or 20,000 IU/kg intramuscularly twice daily. (B626.App.w22)
  • Procaine penicillin G 40,000 IU/kg subcutaneously every 24 hours. (B631.21.w21)
  • 40,000 IU/kg subcutaneously every 24 hours. (B602.41.w41)
  • 20,000 - 40,000 procaine penicillin G IU/kg intramuscularly once or twice daily. (J213.3.w1)
  • Sodium or potasium penicillin G 20,000 IU/kg every four hours subcutaneously, intramuscualrly or intravenously, or 40,000 IU/kg orally. (J213.3.w1)

Great Apes

  • Adult Pan troglodytes - Chimpanzee:
    • Penicillin G benzathine 1,200,000 units by deep intramuscular injection, once. (W768.Jun2012.w1)
    • Penicillin G potassium, 1-20 million  units daily by intravenous or intramuscular injection. (W768.Jun2012.w1)
    • Penicillin G procaine, 22,000 IU/kg by intramuscular injection once daily. (W768.Jun2012.w1)
  • Primates:
    • Penicillin G benzathine 20,000 - 60,000 IU/kg subcutaneously or intramuscularly once daily. (D425.3.15.w3o)
    • Penicillin G potassium 7,000 - 14,000 IU intramuscularly or by slow intravenoous injection three times daily. (D425.3.15.w3o)
    • Penicilin G procaine 50,000 IU/kg subcutaneously once daily. Broad spectrum against Gram-postive organisms and anaerobes. Adequate blood levels are reached by every 24 - 48 hour administration. (D425.3.15.w3o)
Monitoring parameters
  • 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.

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Not for use in patients hypersensitive to penicillins. (B263)
  • Use with caution in patients with documented sensitivity to other beta-lactam antibiotics such as cephalosporins, cefamycins and carbapenems, as there may be cross-reactivity. (B263)
  • Reported sensitivity to procaine penicillin G in snakes, birds, turtles, Guinea pigs, chinchillas). (B263)
  • Oral administration is not appropriate in patients with severe illness such as septicaemia or shock as absorption from the gastrointestinal tract may be significantly diminished or delayed. (B263)
  • Electrolyte imbalances may result from high doses of penicillin G potassium or penicillin G sodium, particularly in small animals with pre-existing electrolyte abnormality, renal disease or congestive heart failure. (B263)
Adverse Effects / Side Effects / Warnings
  • Hypersensitivity reactions:
    • Unrelated to dose. (B263)
    • May result in rash, fever, eosinophilia, neutropaenia, agranulocytosis, thrombocytopaenia, leucopaenia, anaemias, lymphadenopathy.
    • May cause full-blown anaphylaxis. (B263)
  • See: Hypersensitivity angiitis in a Bear
Operator Warnings Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
Overdose / Acute Toxicity --

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects
  • Crosses the placenta; safe use in pregnancy has not been firmly established. (B263)
Teratogenic effects
  • No documented teratogenic effects. (B263)
Mutagenic effects --
Carcinogenic effects

--

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

 

Effects on land  

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Persistence in the Environment
Breakdown in soil and groundwater

 

Breakdown in water  
Breakdown in vegetation  

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