Procaine penicillin formulation

Adverse CNS effects occur when the procaine portion of the procaine benzylpenicillin (procaine penicillin) formulation is given intravascularly. The signs of toxicity include hyperexcitability, muscle tremors, ataxia, apnea and cardiac arrest. There is no specific treatment for procaine toxicity one can only attempt to prevent the horse from injuring itself and others imtil the effects of the procaine wear off. The CNS reaction can be prevented by pretreatment with diazepam. The solubility of the procaine fraction of procaine benzylpenicillin (procaine penicillin) formulations increases with increasing ambient temperature, so these products should be stored in a cool place to reduce the risk of reactions. Procaine is a common cause of positive drug tests in racehorses and other performance horses. Procaine benzylpenicillin (procaine penicillin) should be avoided in these animals. 

In the first example, procaine penicillin, an aqueous vehicle containing the soluble components (such as lecithin, sodium citrate, povidone, and polyoxyethylene sorbitan monooleate) is filtered through a 0.22 pm membrane filter, heat sterilized, and transferred into a presterilized mixing-filling tank. The sterile antibiotic powder, which has previously been produced by freeze-drying, sterile crystallization, or spray-drying, is aseptically added to the sterile solution while mixing. After all tests have been completed on the bulk formulation, it is aseptically filled. 

Depot intramuscular formulations of penicillin G, including procaine penicillin and benzathine penicillin, have decreased solubility, delayed absorption, and a prolonged half-life. Drug concentrations are detectable 24 hours after injection of procaine penicillin, and low levels of benzathine penicillin (0.003 units/mL) are detectable 4 weeks after injection. 

Benzathine and procaine penicillins are formulated to delay absorption, resulting in prolonged blood and tissue concentrations. A single intramuscular injection of 1.2 million units of benzathine penicillin maintains serum levels above 0.02 mcg/mL for 10 days, sufficient to treat B-hemolytic streptococcal infection. After 3 weeks, levels still exceed 0.003 mcg/mL, which is enough to prevent B-hemolytic streptococcal infection. A 600,000 unit dose of procaine penicillin yields peak concentrations of 1-2 mcg/mL and clinically useful concentrations for 12-24 hours after a single intramuscular injection. 

Benzathine penicillin, procaine penicillin Intramuscular, long-acting formulations... 

Sabatini GR, Gulesich JJ. Formulation of a stable and palatable oral suspension of procaine penicillin G. / Am Pharm Assoc (Pract Pharm) 1956 17 806-808. 

Procaine benzylpenicillin (procaine penicillin) is a poorly soluble salt that is absorbed slowly following i.m. or s.c. injection. It is the most commonly used formulation of penicillin in horses. Injections s.c. cause severe local inflammation and hemorrhage, as well as leaving deposits of... 

Benzathine benzylpenicillin is a very insoluble salt. It is administered i.m. in "long-acting" formulations that contain one-half procaine benzylpenicillin (procaine penicillin) and one-half benzathine benzylpenicillin. Any clinical effect is from the procaine benzylpenicillin (procaine penicillin) portion of these formulations since the benzathine penicillin provides persistent but sub-therapeutic plasma concentrations. 

Sometimes, low water solubility is a desirable property and may be useful in the purification of a base after S5m-thesis. It is also of therapeutic use in the formulation of some amines as depot injections, e.g. procaine penicillin (Fig. 3.18). 

Intramuscular Route. The IM route is frequently used for drugs dissolved in oily vehicles or for those in a microcrystalline formulation that are poorly soluble in water (e.g., procaine or penicillin G). Advantages include rapid absorption (often in under 30 min), the opportunity to inject a relatively large amount of solution, and a reduction in pain and local irritation compared with SC injections. Potential comphcations include infections and nerve damage. The latter usually results from the choice of an incorrect site for injection. 

The rates of absorption, clearance, and elimination of penicillin G are influenced by its formulation. Penicillin G is available in a number of different salts either with inorganic ions including sodium, potassium, or calcium or with organic cations including procaine and benzathine. These salts have differing solubilities and hence differing durations of action. 

In contrast to hypersensitivity, other adverse reactions do not require sensitization and require similar doses of drug for recurrence. A special case is a syndrome (Hoigne s syndrome) that resembles an immediate allergic reaction combined with hallucinations, aggressive behavior, anxiety, and auditory and visual disturbances, which has been described after intramuscular procaine penicUhn and benzathine penicillin. It is probably due to accidental intravascular injection and results from micro-embohsm of the penicUhn depot formulation (271-275). 

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