TICARCILLIN DISODIUM
For general information on the penicillins, including adverse effects, contraindications, overdosage, drug interactions and monitoring parameters, refer to the monograph: Penicillins, General Information.
Chemistry - An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with pKas of 2.55 and 3.42. More than 600 mg is solublein 1 ml of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram ofthe disodium contains not less than 800 mg of ticarcillin anhydrous. One gram of the commerciallyavailable injection contains 5.2-6.5 mEq of sodium and after reconstituting the injection has a pH of 6-8.
If stored at room temperature after reconstitution, polymer conjugates can form that may increasethe likelihood of hypersensitivity reactions occurring. Therefore, many clinicians recommend eitherrefrigerating the solution or administering within 30 minutes of reconstitution. From a potencystandpoint, the drug should be used generally within 24 hours if stored at room temperature and 72hours if refrigerated, but the manufacturer has specific recommendations depending on theconcentration of the drug and the solution. Refer to the package insert for more specificrecommendations. Frozen solutions are reportedly stable for at least 30 days when stored at -20°C.
Ticarcillin disodium solutions are reportedly physically compatible with the following solutionsand drugs: D5W, Ringer's Injection, Lactated Ringer's Injection, Sodium chloride 0.9%, Sterilewater for injection, acyclovir sodium, hydromorphone HCl, meperidine HCl, methylprednisolonesodium succinate, morphine Sulfate, ranitidine HCl, perphenazine and verapamil HCl.
Ticarcillin disodium solutions are reportedly physically incompatible with the aminoglycosideantibiotics; refer to the drug interaction information in the Penicillins, General Informationmonograph for more information. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for morespecific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology/Uses, Indications - A ticarcillin disodium product is approved for intrauterine usein horses in the treatment of endometritis in horses caused by beta hemolytic streptococci.
Ticarcillin disodium injection is used in veterinary species in the treatment of systemic
Pseudomonas aeruginosa infections, often in combination with an appropriate aminoglycosideagent. When compared with carbenicillin, ticarcillin is about twice as potent (on a weight basis) inthe treatment against susceptible Pseudomonas. Synergy may occur against some Pseudomonasstrains when used in combination with aminoglycosides, but in vitro inactivation of theaminoglycoside may also occur (see Drug Interactions) if the drugs are physically mixed togetheror in patients with severe renal failure.
Pharmacokinetics (specific) - Ticarcil in is not appreciably absorbed after oral administrationand must be given parenterally to achieve therapeutic serum levels. When given IM to humans, thedrug is readily absorbed with peak levels occurring about 30-60 minutes after dosing. The reportedbioavailability in the horse after IM administration is about 65%. After parenteral injection, ticarcillin is distributed into pleural fluid, interstitial fluid, bile, sputumand bone. Like other penicillins, CSF levels are low in patients with normal meninges (about 6% ofserum levels), but increased (39% of serum levels) if meninges are inflamed. The volume ofdistribution is reportedly 0.34 L/kg in dogs and 0.22-0.25 L/kg in the horse. The drug is 45-65%bound to serum proteins (human). Ticarcillin is thought to cross the placenta and is found in smallquantities in milk. In cattle, mastitic milk levels of ticarcillin are approximately twice those found innormal milk, but are too low to treat most causal organisms.
Ticarcillin is eliminated primarily by the kidneys, via both tubular secretion and glomerular filtration. Concurrent probenecid administration can slow elimination and increase blood levels. Inhumans, about 10-15% of the drug is metabolized by hydrolysis to inactive compounds. The half-life in dogs and cats is reportedly 45-80 minutes and about 54 minutes in the horse. Clearance is4.3 ml/kg/min in the dog and 2.8-3.2 ml/kg/min in the horse.
Chemistry - An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with pKas of 2.55 and 3.42. More than 600 mg is solublein 1 ml of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram ofthe disodium contains not less than 800 mg of ticarcillin anhydrous. One gram of the commerciallyavailable injection contains 5.2-6.5 mEq of sodium and after reconstituting the injection has a pH of 6-8.
Storage, Stability, Compatibility
Ticarcillin injectable powder for injection should be stored attemperatures of less than 30°C (room temperature or colder).If stored at room temperature after reconstitution, polymer conjugates can form that may increasethe likelihood of hypersensitivity reactions occurring. Therefore, many clinicians recommend eitherrefrigerating the solution or administering within 30 minutes of reconstitution. From a potencystandpoint, the drug should be used generally within 24 hours if stored at room temperature and 72hours if refrigerated, but the manufacturer has specific recommendations depending on theconcentration of the drug and the solution. Refer to the package insert for more specificrecommendations. Frozen solutions are reportedly stable for at least 30 days when stored at -20°C.
Ticarcillin disodium solutions are reportedly physically compatible with the following solutionsand drugs: D5W, Ringer's Injection, Lactated Ringer's Injection, Sodium chloride 0.9%, Sterilewater for injection, acyclovir sodium, hydromorphone HCl, meperidine HCl, methylprednisolonesodium succinate, morphine Sulfate, ranitidine HCl, perphenazine and verapamil HCl.
Ticarcillin disodium solutions are reportedly physically incompatible with the aminoglycosideantibiotics; refer to the drug interaction information in the Penicillins, General Informationmonograph for more information. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for morespecific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology/Uses, Indications - A ticarcillin disodium product is approved for intrauterine usein horses in the treatment of endometritis in horses caused by beta hemolytic streptococci.
Ticarcillin disodium injection is used in veterinary species in the treatment of systemic
Pseudomonas aeruginosa infections, often in combination with an appropriate aminoglycosideagent. When compared with carbenicillin, ticarcillin is about twice as potent (on a weight basis) inthe treatment against susceptible Pseudomonas. Synergy may occur against some Pseudomonasstrains when used in combination with aminoglycosides, but in vitro inactivation of theaminoglycoside may also occur (see Drug Interactions) if the drugs are physically mixed togetheror in patients with severe renal failure.
Pharmacokinetics (specific) - Ticarcil in is not appreciably absorbed after oral administrationand must be given parenterally to achieve therapeutic serum levels. When given IM to humans, thedrug is readily absorbed with peak levels occurring about 30-60 minutes after dosing. The reportedbioavailability in the horse after IM administration is about 65%. After parenteral injection, ticarcillin is distributed into pleural fluid, interstitial fluid, bile, sputumand bone. Like other penicillins, CSF levels are low in patients with normal meninges (about 6% ofserum levels), but increased (39% of serum levels) if meninges are inflamed. The volume ofdistribution is reportedly 0.34 L/kg in dogs and 0.22-0.25 L/kg in the horse. The drug is 45-65%bound to serum proteins (human). Ticarcillin is thought to cross the placenta and is found in smallquantities in milk. In cattle, mastitic milk levels of ticarcillin are approximately twice those found innormal milk, but are too low to treat most causal organisms.
Ticarcillin is eliminated primarily by the kidneys, via both tubular secretion and glomerular filtration. Concurrent probenecid administration can slow elimination and increase blood levels. Inhumans, about 10-15% of the drug is metabolized by hydrolysis to inactive compounds. The half-life in dogs and cats is reportedly 45-80 minutes and about 54 minutes in the horse. Clearance is4.3 ml/kg/min in the dog and 2.8-3.2 ml/kg/min in the horse.