CLINICAL PHARMACOLOGY
Penicillin G procaine is an equimolecular compound of procaine and penicillin G, administered intramuscularly as a suspension. It dissolves slowly at the site of injection, giving a plateau type of blood level at about 4 hours which falls slowly over a period of the next 15 to 20 hours.
Approximately 60% of penicillin G is bound to serum protein. The drug is distributed throughout the body tissues in widely varying amounts. Highest levels are found in the kidneys with lesser amounts in the liver, skin, and intestines. Penicillin G penetrates into all other tissues to a lesser degree with a very small level found in the cerebrospinal fluid. With normal kidney function, the drug is excreted rapidly by tubular excretion. In neonates and young infants and in individuals with impaired kidney functions, excretion is considerably delayed. Approximately 60 to 90 percent of a dose of parenteral penicillin G is excreted in the urine within 24 to 36 hours.
Microbiology: Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been documented. Penicillin G exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (Groups A, C, G, H, L, and M), and pneumococci. Other organisms susceptible to penicillin G are Corynebacterium diphtheriae, Bacillus anthracis, Clostridium species, Actinomyces bovis, Streptobacillus moniliformis, Listeria monocytogenes, and Leptospira species. Treponema pallidum is extremely susceptible to the bactericidal action of penicillin G.
Susceptibility Testing
Ten unit Penicillin G Susceptibility Discs may be used to determine microbial susceptibility to penicillin G using one of the followingstandard methods recommended by the National Committee for Laboratory Standards:
M2-T4,“Performance Standards for Antimicrobial Disc Susceptibility Tests”
M7-T2,“Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically”
Tests should be interpreted by the following criteria:
Zone Diameter, nearest whole mm | Susceptible | Moderately
Susceptible | Resistant |
| Staphylococci | ≥29 | - | ≤28 |
| Enterococci | - | ≥15 | ≤14 |
| L. monocytogenes | ≥20 | - | ≤19 |
| Non-enterococcal streptococci | ≥28 | 20–27 | ≤19 |
Approximate MIC Correlates | Susceptible | Resistant |
| Staphylococci | ≤0.1 μg/mL | β-lactamase |
| Enterococci | - | ≥16 μg/mL |
| L. monocytogenes | ≤2 μg/mL | ≥4 μg/mL |
| Non-enterococcal streptococci | ≤0.12 μg/mL | ≥4 μg/mL |
Interpretations of susceptible, intermediate, and resistant correlate zone size diameters with MIC values. A laboratory report of “susceptible” indicates that the suspected causative microorganism most likely will respond to therapy with penicillin G. A laboratory report of “resistant” indicates that the infecting microorganism most likely will not respond to therapy. A laboratory report of “moderately susceptible” indicates that the microorganism is most likely susceptible if a high dosage of penicillin G is used, or if the infection is such that high levels of penicillin G may be attained as in urine. A report of “intermediate” using the disc diffusion method may be considered an equivocal result, and dilution tests may be indicated.
Control organisms are recommended for susceptibility testing. Each time the test is performed the following organism should be included. The range for zones of inhibition is shown below:
| Control Organism | Zone of Inhibition Range |
| Staphylococcus aureus | 26–37 |
| (ATCC 25923) | |
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