With procaine-penicillin

Administration of streptomycin intramuscularly is the method of choice for treating systemic infections. Oral forms of streptomycin or dihydrostreptomycin, frequently combined with sulfonamide drugs and other compounds, are also used in animals for treatment of enteric infections. In addition, streptomycin is used as a feed additive for growth promotion purposes. In some countries, the combination of streptomycin with procaine penicillin is used as an initial nonspecific therapy in farm animals, and in intramammary applications for treatment of mastitis. Intramuscular dosages are in the range 5-10 mg/kg bw, while oral dosages are 20 mg/kg bw. Dihydrostreptomycin is also used in veterinary medicine in intramammary and topical treatments. 

Kraus SJ, Green RL. Pseudoanaphylactic reactions with procaine penicillin. Cutis 1976 17(4) 765-7. 

Antimicrobial treatment should be limited to those who have clinical and epidemiologic features of group A streptococcal pharyngitis with a positive laboratory test. Penicillin is the drug of choice in the treatment of group A streptococcal pharyngitis (Table 107-8). It has the narrowest spectrum of activity, and it is effective, safe, and inexpensive. The only controlled studies that have demonstrated that antimicrobial therapy prevents rheumatic fever were done with procaine penicillin, which was later replaced with benzathine penicillin. " ... 

The goal of treatment of erysipelas is rapid eradication of the infection. Mild to moderate cases of erysipelas are treated with procaine penicillin G 600,000 units intramuscularly twice daily or penicillin VK 250-500 mg orally four times daily (in children 1-18 years of age, 25,000-90,000 units/kg per day divided into four doses) for 7 to 10 days. " Penicillin-allergic patients can be treated with clindamycin 150-300 mg orally every 6 to 8 hours (in children, 10-30 mg/ kg per day in three to four divided doses). For more serious infections, the patient should be hospitalized, and aqueous penicillin G 2-8 million units daily should be administered intravenously. Marked improvement usually is seen within 48 hours, and the patient often may be switched to oral penicillin to complete the course of therapy. One randomized, double-blind, placebo-controlled study showed that the median time for cure, intravenous antibiotics, and hospital stay was reduced in patients receiving prednisolone in addition to antibiotics. Further studies are needed, however, before corticosteroids can be recommended for routine use/- ... 

Pharmacologic effects of the dmg or toxin (eg, procaine reaction with procaine penicillin). 

Examples of reversible breakdown of structure have been reported for procaine penicillin dispersions (7), for model systems of calcium carbonate in polybutene ( ), and for numerous other systems. During shear the particles are forced into contact with each other with sufficient kinetic energy to overcome any natural barrier against their displacement of a lyosphere around each individual particle. A dispersion which is inherently stable can thus be forced by shear into a condition of instability. 

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

As streptococcal cellulitis is indistinguishable clinically from staphylococcal cellulitis, administration of a semisynthetic penicillin (nafrillin or oxacillin) or first-generation cephalosporin (cefazolin) is recommended until a definitive diagnosis, by skin or blood cultures, can be made (Table 47-4). If documented to be a mild cellulitis secondary to streptococci, oral penicillin VK, or intramuscular procaine penicillin may be administered. More severe streptococcal infections should be treated with IV antibiotics (such as ceftriaxone 50 to 100 mg/kg as a single dose). 

Gonococcal infection Procaine penicillin along with probenecid can be used. 

The rates of absorption, clearance, and elimination of penicillin G are further influenced by the route of administration. Intramuscular and subcutaneous injections provide drug to the bloodstream more slowly, but maintain concentrations longer than the intravenous administration. Absorption of penicillin G from intramuscular or subcutaneous sites can be further slowed down by the use of the relatively insoluble procaine salt. When equivalent dosages of penicillin G and procaine penicillin G were injected parenterally, peak residues concentration in blood occurred after 2 h and the drug had cleared the blood by 8 following penicillin G administration. With the procaine penicillin G, peak residues concentration appeared 5 h after injection and the drug cleared the plasma 24 h after administration (57). 

Apart from the pathophysiological condition of the animal, the mode of drug application may also significantly influence the pharmacokinetic profile of a drug (48, 49). For example, drug residues may persist at the injection site for prolonged periods of time (2). In a study in which various sulfonamides and trimethoprim were injected intramuscularly into swine, detectable residues were found at most sites 6 days after the injection, and with the sulfonamides at 30 days in almost half of the animals (50). Other drugs such as dihydrostreptomycin persist for up to 60 days, while positive residues of chloramphenicol are found at 7 days postinjection. Sodium and procaine penicillin, neomycin, tylosin, and oxytetracycline residues have also been determined at 24 h or more postinjection (51). 

Parenteral preparations with antimicrobial activity, which depends on the causative pathogenic microorganism, and pharmacokinetic properties that meet most of these criteria include procaine penicillin G (aqueous suspension), amoxicillin trihydrate-clavulanate potassium combination (aqueous suspension), and enro-floxacin (solution). Enrofloxacin is not approved for use... 

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. 

The potentiated sulfonamides have been associated with producing diarrhea in horses. In one study, changes in coliforms and clostridia were not seen following p.o. administration of trimethoprim/sulfadiazine. However, in a study of hospitalized horses, the risk of diarrhea was significantly increased when horses had been given a potentiated sulfonamide and procaine benzyl-penicillin (procaine penicillin) concurrently. 

Many of the medical products reviewed here find multiple applications. Thus procaine compounded with benzylpenicillin, penicillin G is an antimicrobial veterinary drug, approved in the US as a postexposure prophylaxis following inhalation of anthrax, providing that the strains do not have penicillin resistance. 

Fig. 2.9 Mean plasma penicillin concentration-time curves after 20 000IU of procaine penicillin G per kilogram was administered to five animals (four horses and one pony) at five different sites. (Reproduced with permission from Firth et al. (1986).)...

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