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Penicillin G (Penicillin G Potassium) - Description and Clinical Pharmacology


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To reduce the development of drug-resistant bacteria and maintain the effectiveness of Penicillin G Potassium for Injection, USP and other antibacterial drugs, Penicillin G Potassium for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.


Penicillin G Potassium for Injection, USP is a natural penicillin. Penicillin G Potassium for Injection, USP is a sterile, pyrogen-free powder for reconstitution. Penicillin G Potassium for Injection, USP is an antibacterial agent intended for parenteral administration.

Chemically, Penicillin G Potassium for Injection, USP is monopotassium (2S,5R,6R) -3,3-dimethyl-7- oxo-6- (2-phenylacetamido) -4-thia-1- azabicyclo (3.2.0) heptane-2-carboxylate. It has a molecular weight of 372.48 and the following structural formula:

Penicillin G potassium is a colorless or white crystal, or a white crystalline powder which is odorless, or practically so, and moderately hygroscopic. Penicillin G potassium is very soluble in water. The pH of the reconstituted product is between 6.0-8.5. Penicillin G potassium is buffered with sodium citrate to an optimum pH.

Penicillin G Potassium for Injection, USP is supplied in vials equivalent to 1,000,000 units (1 million units), 5,000,000 units (5 million units), for intramuscular and intravenous use or 20,000,000 units (20 million units), for intravenous use only, of penicillin G as the potassium salt. Each million units contains approximately 6.9 milligrams of sodium (0.3 mEq) and 65.8 milligrams of potassium (1.68 mEq).


After an intravenous infusion of penicillin G, peak serum concentrations are attained immediately after completion of the infusion. In a study of ten patients administered a single 5 million unit dose of penicillin G intravenously over 3 to 5 minutes, the mean serum concentrations were 400 mcg/mL, 273 mcg/mL and 3 mcg/mL at 5 to 6 minutes, 10 minutes and 4 hours after completion of the injection, respectively. In a separate study, five healthy adults were administered one million units of penicillin G intravenously, either as a bolus over 4 minutes or as an infusion over 60 minutes. The mean serum concentration eight minutes after completion of the bolus was 45 mcg/mL and eight minutes after completion of the infusion was 14.4 mcg/mL. The mean β-phase serum half-life of penicillin G administered by the intravenous route in ten patients with normal renal function was 42 minutes, with a range of 31 to 50 minutes.

The clearance of penicillin G in normal individuals is predominantly via the kidney. The renal clearance, which is extremely rapid, is the result of glomerular filtration and active tubular transport, with the latter route predominating. Urinary recovery is reported to be 58 to 85% of the administered dose. Renal clearance of penicillin is delayed in premature infants, neonates and in the elderly due to decreased renal function. The serum half-life of penicillin G correlates inversely with age and clearance of creatinine and ranges from 3.2 hours in infants 0 to 6 days of age to 1.4 hours in infants 14 days of age or older.

Nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion. The latter routes become more important with renal impairment.

Probenecid blocks the renal tubular secretion of penicillin. Therefore, the concurrent administration of probenecid prolongs the elimination of penicillin G and, consequently, increases the serum concentrations.

Penicillin G is distributed to most areas of the body including lung, liver, kidney, muscle, bone and placenta. In the presence of inflammation, levels of penicillin in abscesses, middle ear, pleural, peritoneal and synovial fluids are sufficient to inhibit most susceptible bacteria. Penetration into the eye, brain, cerebrospinal fluid (CSF) or prostate is poor in the absence of inflammation. With inflamed meninges, the penetration of penicillin G into the CSF improves, such that the CSF/serum ratio is 2 to 6%. Inflammation also enhances its penetration into the pericardial fluid. Penicillin G is actively secreted into the bile resulting in levels at least 10 times those achieved simultaneously in serum. Penicillin G penetrates poorly into human polymorphonuclear leukocytes.

In the presence of impaired renal function, the β-phase serum half-life of penicillin G is prolonged. β-phase serum half-lives of one to two hours were observed in azotemic patients with serum creatinine clearance concentrations <3 mg/100 mL and ranged as high as 20 hours in anuric patients. A linear relationship, including the lowest range of renal function, is found between the serum elimination rate constant and renal function as measured by creatinine clearance.

In patients with altered renal function, the presence of hepatic insufficiency further alters the elimination of penicillin G. In one study, the serum half-lives in two anuric patients (excreting <400 mL urine /day) were 7.2 and 10.1 hours. A totally anuric patient with terminal hepatic cirrhosis had a penicillin half-life of 30.5 hours, while another patient with anuria and liver disease had a serum half-life of 16.4 hours. The dosage of the penicillin G should be reduced in patients with severe renal impairment, with additional modifications when hepatic disease accompanies the renal impairment. Hemodialysis has been shown to reduce penicillin G serum levels.


Penicillin G is bactericidal against penicillin-susceptible microorganisms during the stage of active multiplication. It acts by inhibiting biosynthesis of cell-wall mucopeptide. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. Penicillin G is highly active in vitro against staphylococci (except penicillinase- producing strains), streptococci (groups A, B, C, G, H, L, and M), pneumococci and Neisseria meningitidis.

Other organisms susceptible in vitro to penicillin G are Neisseria gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, clostridia, Actinomyces species, Spirillum minus, Streptobacillus moniliformis, Listeria monocytogenes, and leptospira;Treponema pallidum is extremely susceptible. Some species of gram-negative bacilli were previously considered susceptible to very high intravenous doses of penicillin G (up to 80 million units/day) including some strains of Escherichia coli, Proteus mirabilis, salmonella, shigella, Enterobacter aerogenes (formerly Aerobacter aerogenes) and Alcaligenes faecalis. Penicillin G is no longer considered a drug of choice for infections caused by these organisms.

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community–acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on dilution method1,2 (broth, agar or microdilution) or equivalent using standardized inoculum and concentrations of penicillin. The MIC values should be interpreted according to the criteria in Table 1.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 10 units of penicillin to test the susceptibility of microorganisms to penicillin. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for penicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 unit penicillin disk should be interpreted according to the following criteria in Table 1.

Table 1. Susceptibility Test Interpretive Criteria for Penicillin2,4
MIC (mcg/mL) Disk Diffusion (zone diameter in mm) 1
Pathogen Susceptible (S) Intermediate (I) Resistant (R) Susceptible (S) Intermediate (I) Resistant (R)
Staphylococci ≤0.12 2 - ≥0.25 ≥29 - ≤28


gonorrhoeae 3

≤0.06 0.12 -1 ≥2 ≥47 27 – 46 ≤26




≤0.06 - ≥0.12 - - -




≤2 4 ≥8 - - -


streptococci 4

≤0.12a - - ≥24 5 - -

Streptococcus spp.

Viridans group

≤0.12 0.25 – 2 ≥4 - - -



≤2 - - - - -
Bacillus anthracis 6 <0.12 - >0.25 - - -

1 Organisms for which no values for disk susceptibility appear cannot be reliably tested with this method.
2 Penicillin-resistant strains of staphylococci produce β-lactamase. An induced β-lactamasetest should be performed on all S. aureus isolates for which the penicillin MIC is <0.12 mcg/mL or zone diameter is >29 mm before reporting as penicillin susceptible. Rare isolates of staphylococci that contain genes for β-lactamase production may not produce a positive induced β-lactamase test. For serious infections requiring penicilin therapy, laboratories should perform MIC tests and induced β-lactamase testing on all subsequent isolates from the same patient.2
3 A positive N. gonorrhoeae β-lactamase test predicts one form of resistance to penicillin. Strains with chromosomally mediated resistance can be detected only by agar dilution or disk diffusion susceptibility test methods.2 Isolates with zone diameters <19 mm generally produce β-lactamase.2,3
4 Susceptibility testing of penicillins for treatment of β-hemolytic streptococcal infectionsneed not be performed routinely, because non-susceptible isolates are extremely rare inany ®-hemolytic streptococcus and have not been reported from Streptococcus pyogenes.Any ®-hemolytic streptococcal isolate found to be non-susceptible to penicillin should be re-identified, retested, and, if confirmed, submitted to a public health authority.2,3
5 The current absence of resistant isolates precludes defining results other than "Susceptible". Isolates yielding results suggestive of "Nonsusceptible" should be submitted to a reference laboratory for further testing.
6 B. anthracis strains may contain inducible β-lactamases. In vitro penicillinase induction studies suggest that penicillin MICs may increase during therapy. However, β-lactamase testing of clinical isolates of B. anthracis is unreliable and should not be performed.4

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard penicillin powder should provide MIC values provided below. For the diffusion technique, the 10 unit penicillin disk should provide the following zone diameters with the quality control strains:

Table 2. In vitro Susceptibility Test Quality Control Ranges for Penicillin
Organism (ATCC® #)

MIC range


Disk Diffusion

range (mm)

Staphylococcus aureus (29213) 0.25 -2 Not applicable
Staphylococcus aureus (25923) Not applicable 26 -37
Streptococcus pneumoniae (49619) 0.25 -1 24 – 30
Neisseria gonorrhoeae (49226) 0.25 -1 1 26 – 34

1 Using agar dilution method only. No criteria for broth microdilution are available.2

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