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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 soluble in 1 ml of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram of the disodium contains not less than 800 mg of ticarcillin anhydrous. One gram of the commercially available 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 at temperatures of less than 30°C (room temperature or colder).
If stored at room temperature after reconstitution, polymer conjugates can form that may increase the likelihood of hypersensitivity reactions occurring. Therefore, many clinicians recommend either refrigerating the solution or administering within 30 minutes of reconstitution. From a potency standpoint, the drug should be used generally within 24 hours if stored at room temperature and 72 hours if refrigerated, but the manufacturer has specific recommendations depending on the concentration of the drug and the solution. Refer to the package insert for more specific recommendations. 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 solutions and drugs: D5W, Ringer’s Injection, Lactated Ringer’s Injection, Sodium chloride 0.9%, Sterile water for injection, acyclovir sodium, hydromorphone HCl, meperidine HCl, methylprednisolone sodium succinate, morphine Sulfate, ranitidine HCl, perphenazine and verapamil HCl.
Ticarcillin disodium solutions are reportedly physically incompatible with the aminoglycoside antibiotics; refer to the drug interaction information in the Penicillins, General Information monograph for more information. 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/Uses/Indications – A ticarcillin disodium product is approved for intrauterine use in 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 aeruginosainfections, often in combination with an appropriate aminoglycoside agent. When compared with carbenicillin, ticarcillin is about twice as potent (on a weight basis) in the treatment against susceptible Pseudomonas. Synergy may occur against some Pseudomonas strains when used in combination with aminoglycosides, but in vitro inactivation of the aminoglycoside may also occur (see Drug Interactions) if the drugs are physically mixed together or in patients with severe renal failure.
Pharmacokinetics (specific) – Ticarcillin is not appreciably absorbed after oral administration and must be given parenterally to achieve therapeutic serum levels. When given IM to humans, the drug is readily absorbed with peak levels occurring about 30-60 minutes after dosing. The reported bioavailability in the horse after IM administration is about 65%.
After parenteral injection, ticarcillin is distributed into pleural fluid, interstitial fluid, bile, sputum and bone. Like other penicillins, CSF levels are low in patients with normal meninges (about 6% of serum levels), but increased (39% of serum levels) if meninges are inflamed. The volume of distribution 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 small quantities in milk. In cattle, mastitic milk levels of ticarcillin are approximately twice those found in normal 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. In humans, 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 is 4.3 ml/kg/min in the dog and 2.8-3.2 ml/kg/min in the horse.
For susceptible systemic infections:
a) 44 mg/kg q5h IV or tid IM. (Robinson 1987)
b) Foals: 50 mg/kg IV q6-8h (Dose extrapolated from data obtained from adult horses; use lower dose or longer interval in premature foals or those less than 7 days old.) (Caprile and Short 1987)
For treatment of endometritis secondary to susceptible bacteria:
a) 6 grams intrauterine per day for 3 days during estrus. Reconstitute vial with 25 ml of Sterile Water for Injection, USP or Sodium Chloride Injection, USP. After dissolved, further dilute to a total volume of 100-500 ml with sterile water or sterile normal saline and aseptically instill into uterus. (Package insert; Ticillin®—Beecham)
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Ticarcillin Disodium Sterile Powder for Intrauterine Infusion 6 g vial; Ticillin® (Pfizer); (Rx) Approved for use in horses.
Ticarcillin Disodium Powder for Injection (contains 5.2 mEq sodium./g) 1 g, 3 g, 6 g, 20 g, & 30 g in vials; Ticar® (SK-Beecham); (Rx)
Also available with human approval is a ticarcillin/clavulanic acid injectable preparation (Timentin® —Beecham) that would be effective against many penicillinase-producing strains of bacteria, such as most Staphylococcus species.