2. Only after the production of penicillin had increased enough to make low-priced penicillin available did the oral dosage forms become popular. --The water-soluble potassium and sodium salts are used orally and parenterally to achieve high plasma concentrations of penicillin G rapidly. The more water-soluble potassium salt usually is preferred when large doses are required. --Situations in which hyperkalemia is a danger, however, as in renal failure, require use of the sodium salt; the potassium salt is preferred for patients on salt-free diets or with congestive heart conditions

4. The rapid elimination of penicillin from the bloodstream through the kidneys by active tubular secretion and the need to maintain an effective concentration in blood have led to the development of “repository” forms of this drug. Suspensions of penicillin in peanut oil or sesame oil with white beeswax added were first used to prolong the duration of injected forms of penicillin. --This dosage form was replaced by a suspension in vegetable oil, to which aluminum monostearate or aluminum distearate was added. Today, most repository forms are suspensions of high–molecular weight amine salts of penicillin in a similar base.

5. 2-Penicillin G Procaine The first widely used amine salt of penicillin G was made with procaine. Penicillin G procaine (Crysticillin,Duracillin, Wycillin) can be made readily from penicillin G sodium by treatment with procaine hydrochloride. This salt is considerably less soluble in water than the alkali metal salts, requiring about 250 mL to dissolve 1 g. Free penicillin is released only as the compound dissolves and dissociates. Some commercial products are mixtures of penicillin G potassium or sodium with penicillin G procaine; the water-soluble salt provides rapid development of a high plasma concentration of penicillin, and the insoluble salt prolongs the duration of effect.