Procaine salt

The activity of penicillin G was originally defined in units. Crystalline sodium penicillin G contains approximately 1600 units per mg (1 unit = 0.6 meg 1 million units of penicillin = 0.6 g). Semisynthetic penicillins are prescribed by weight rather than units. The minimum inhibitory concentration (MIC) of any penicillin (or other antimicrobial) is usually given in mcg/mL. Most penicillins are dispensed as the sodium or potassium salt of the free acid. Potassium penicillin G contains about 1.7 mEq of K+ per million units of penicillin (2.8 mEq/g). Nafcillin contains Na +, 2.8 mEq/g. Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for years at 4°C. Solutions lose their activity rapidly (eg, 24 hours at 20°C) and must be prepared fresh for administration. 

The sodium and potassium salts are rapidly absorbed but give effective plasma concentrations for no more than 4 h. The procaine salt has a lower solubility and forms, on injection, a depot that slowly releases penicillin G, maintaining effective concentrations for up to 24 h. After intramuscular treatment of swine... 

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). 

Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for long periods (eg, for years at 4 °C). Solutions lose their activity rapidly (eg, 24 hours at 20 °C) and must be prepared fresh for administration. 

Procaine salt, CMHMN404Sj, crystals from water. 

Benzathine salts have particularly low aqueous solubility and, when injected intramuscularly, form a depot from which dissolution occurs slowly. Indeed, all benzathine benzylpenicillin salts have been banned from use in the food-producing animals in the EU, because of persistence at and erratic rate of depletion from injection sites and a consequent perceived hazard to human health. Procaine salts, on the other hand, are somewhat more water-soluble and remain in widespread use, formulated as aqueous or oily suspensions. These formulations provide flip-flop pharmacokinetics with terminal half-lives in the range of 8.9-17.0 h after intramuscular or subcutaneous dosing to calves and adult cattle. In some studies, absorption... 

Fig. 48. t — X diagrams for the binary systems of four procaine salts with water. 

Summarising we may therefore consider these and similar demixings in binary systems H2O + salt as complex coacervation reduced to its simplest form beside water only the two essential ions are present these in the case of procaine salts are only monovalent and do not even possess macromolecular structure. 

The water-poorest complex coacervate (pH == 3.5, mixing proportion 50%) only contains about 18% colloids, thus more than 80% water. From the dis rams of Fig. 48 we read off for the procaine salt-rich layer at 20° on the other hand a salt content of about 75—85% and this layer therefore contains only 15— 25% water. 

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