AMPICILLIN, AMPICILLIN SODIUM, AMPICILLIN TRIHYDRATE
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 aspractically 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/mlvs. 6 mg/ml at 20°C). Ampicillin anhydrous or trihydrate oral suspensions have a pH of 5-7.5 afterreconstitution with water.
Ampicillin sodium occurs as an odorless or practically odorless, white to off-white, crystallinehygroscopic 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 availableampicillin 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 mayalso be known as aminobenzylpenicillin, AY-6108, or BRL 1341.
Ampicillin trihydrate for injection (Polyflex®) is stable for 12 months if refrigerated (2-8°C) and isstable for 3 months when kept at room temperature.
Ampicillin sodium for injection is relatively unstable after reconstitution and should generally beused within 1 hour of reconstitution. As the concentration of the drug in solution increases, thestability of the drug decreases. Dextrose may also speed the destruction of the drug by acting as acatalyst in the hydrolysis of ampicillin.
While most sources recommend using solutions of ampicillin sodium immediately, studies havedemonstrated that at concentrations of 30 mg/ml, ampicillin sodium solutions are stable in sterilewater for injection or 0.9% sodium chloride for up to 48 hours (72 hours if concentrations are 20mg/ml or less) if kept at 4°C. Solutions with a concentration of 30 mg/ml or less have also beenshown 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 paragraphfor 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).
Uses, Indications - In dogs and cats, ampicillin is not as well absorbed after oral administration asis amoxicillin and its oral use has largely been supplanted by amoxicillin. It is used commonly inparenteral dosage forms when an aminopenicillin is indicated in all species.
Pharmacokinetics (specific) - Ampicillin anhydrous and trihydrate is relatively stable in thepresence of gastric acid. After oral administration, it is about 30-55% absorbed in humans (emptystomach) 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 dosageform 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 humansand 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 crossinto the CSF when meninges are inflamed in concentrations that may range from 10-60% of thosefound in serum. Very low levels of the drug are found in the aqueous humor and low levels arefound in tears, sweat and saliva. Ampicillin crosses the placenta, but is thought to be relatively safeto use during pregnancy. Ampicillin is approximately 20% bound to plasma proteins, primarilyalbumin. Milk levels of ampicillin are considered to be low.
Ampicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, butsome of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in theurine. Elimination half-lives of ampicillin have been reported as 45-80 minutes in dogs and cats, and60 minutes in swine.
Chemistry - A semi-synthetic aminopenicillin, ampicillin anhydrous and trihydrate occur aspractically 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/mlvs. 6 mg/ml at 20°C). Ampicillin anhydrous or trihydrate oral suspensions have a pH of 5-7.5 afterreconstitution with water.
Ampicillin sodium occurs as an odorless or practically odorless, white to off-white, crystallinehygroscopic 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 availableampicillin 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 mayalso be known as aminobenzylpenicillin, AY-6108, or BRL 1341.
Storage, Stability, Compatibility
Ampicillin anhydrous or trihydrate capsules and powder fororal suspension should be stored at room temperature (15-30°C). After reconstitution, the oralsuspension 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 isstable for 3 months when kept at room temperature.
Ampicillin sodium for injection is relatively unstable after reconstitution and should generally beused within 1 hour of reconstitution. As the concentration of the drug in solution increases, thestability of the drug decreases. Dextrose may also speed the destruction of the drug by acting as acatalyst in the hydrolysis of ampicillin.
While most sources recommend using solutions of ampicillin sodium immediately, studies havedemonstrated that at concentrations of 30 mg/ml, ampicillin sodium solutions are stable in sterilewater for injection or 0.9% sodium chloride for up to 48 hours (72 hours if concentrations are 20mg/ml or less) if kept at 4°C. Solutions with a concentration of 30 mg/ml or less have also beenshown 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 paragraphfor 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, AMPICILLIN SODIUM, AMPICILLIN TRIHYDRATE
Ampicillin and the other aminopenicillins have increased activity against manystrains 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 naturalpenicillins they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staphaureus). Although not as active as the natural penicillins, they do have activity against manyanaerobic bacteria, including Clostridial organisms. Organisms that are generally not susceptibleinclude Pseudomonas aeruginosa, Serratia, Indole-positive Proteus (Proteus mirabilis issusceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactiveagainst Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses.Uses, Indications - In dogs and cats, ampicillin is not as well absorbed after oral administration asis amoxicillin and its oral use has largely been supplanted by amoxicillin. It is used commonly inparenteral dosage forms when an aminopenicillin is indicated in all species.
Pharmacokinetics (specific) - Ampicillin anhydrous and trihydrate is relatively stable in thepresence of gastric acid. After oral administration, it is about 30-55% absorbed in humans (emptystomach) 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 dosageform 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 humansand 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 crossinto the CSF when meninges are inflamed in concentrations that may range from 10-60% of thosefound in serum. Very low levels of the drug are found in the aqueous humor and low levels arefound in tears, sweat and saliva. Ampicillin crosses the placenta, but is thought to be relatively safeto use during pregnancy. Ampicillin is approximately 20% bound to plasma proteins, primarilyalbumin. Milk levels of ampicillin are considered to be low.
Ampicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, butsome of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in theurine. Elimination half-lives of ampicillin have been reported as 45-80 minutes in dogs and cats, and60 minutes in swine.