Sorry, you need to enable JavaScript to visit this website.

PFIZERPEN® (penicillin G potassium) Clinical Pharmacology

CLINICAL PHARMACOLOGY

Aqueous penicillin G is rapidly absorbed following both intramuscular and subcutaneous injection. Initial blood levels following parenteral administration are high but transient. Penicillins bind to serum proteins, mainly albumin. Therapeutic levels of the penicillins are easily achieved under normal circumstances in extracellular fluid and most other body tissues. Penicillins are distributed in varying degrees into pleural, pericardial, peritoneal, ascitic, synovial, and interstitial fluids. Penicillins are excreted in breast milk. Penetration into the cerebrospinal fluid, eyes, and prostate is poor. Penicillins are rapidly excreted in the urine by glomerular filtration and active tubular secretion, primarily as unchanged drug. Approximately 60 percent of the total dose of 300,000 units is excreted in the urine within this 5-hour period. For this reason, high and frequent doses are required to maintain the elevated serum levels desirable in treating certain severe infections in individuals with normal kidney function. In neonates and young infants, and in individuals with impaired kidney function, excretion is considerably delayed.

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 3–5 minutes, the mean serum concentrations were 400 mcg/mL, 273 mcg/mL and 3.0 mcg/mL at 5–6 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 31–50 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 58–85% 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 in 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 2–6%. 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 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 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.

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 peptidoglycan rendering the cell wall osmotically unstable. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci or against organisms resistant to beta-lactams because of alterations in the penicillin-binding proteins, such as methicillin-resistant staphylococci. Penicillin G is highly active in vitro against streptococci (groups A, B, C, G, H, L and M) and Neisseria meningitidis.

Other organisms susceptible to penicillin G are N. gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, Clostridium spp., Actinomyces species, "Spirillum minus", Streptobacillus moniliformis, Listeria monocytogenes and Leptospira spp.; Treponema pallidum is extremely sensitive to the bactericidal action of penicillin G.

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 spp. and Shigella spp.; 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 Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

What's New

No Current Announcements.

Therapeutic Area

Contact Pfizer Medical

Report an Adverse Event
1-800-438-1985

Contact Pfizer

Need to report an Adverse Event, Side Effect or Product Quality Concern?

Contact Pfizer Safety to report an adverse event, side effect or concern about the quality of a Pfizer product: (800) 438-1985

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns at 1-800-FDA-1088 or www.fda.gov/MedWatch

Have a Medical Question on a Pfizer Prescription Medicine?
Contact Pfizer Medical Information to speak with a professional regarding your medical question on a Pfizer prescription product: (800) 438-1985
Have a Question about Pfizer Clinical Trials?
If you are looking for information about Pfizer studies currently recruiting new patients in your area, you can begin your search on our website. For questions about a Pfizer Clinical Trial, call (800) 718-1021 or email [email protected]
Need Information on Pfizer’s Patient Assistance Programs?

Pfizer RxPathways® connects eligible patients, regardless of their insurance status, to a range of assistance programs that offer insurance support, co-pay help, and medicines for free or at a savings. For more information, please call (844) 989-7284 or visit www.PfizerRxPathways.com.

Eligible patients can register for valuable savings offers for nearly 40 brand name medications. Visit www.MyPfizerBrands.com for more information.