indication

For use in the treatment of severe infections caused by penicillin G-susceptible microorganisms when rapid and high penicillin levels are required such as in the treatment of septicemia, meningitis, pericarditis, endocarditis and severe pneumonia.

pharmacology

Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that penicillin G interferes with an autolysin inhibitor.

toxicity

Oral LD₅₀ in rat is 8900 mk/kg. Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta-lactams. Neutropenia can occur if high doses are administered consistently for over 2 weeks.

biotransformation

About 16-30% of an intramuscular dose is metabolized to penicilloic acid, an inactive metabolite. Small amounts of 6-aminopenicillanic acid have been recovered in the urine of patients on penicillin G. A small percentage of the drug appears to be hydroxylated into one or more active metabolites, which are also excreted via urine.

absorption

Rapidly absorbed following both intramuscular and subcutaneous injection. Initial blood levels following parenteral administration are high but transient. Oral absorption in fasting, healthy humans is only about 15-30% as it is very susceptible to acid-catalyzed hydrolysis.

half life

In adults with normal renal function is reportedly 0.4–0.9 hours

route of elimination

Penicillin G is eliminated by the kidneys. Nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion.

drug interactions

Demeclocycline: Possible antagonism of action

Doxycycline: Possible antagonism of action

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Mestranol: This anti-infectious agent could decreases the effect of the oral contraceptive

Methacycline: Possible antagonism of action

Methotrexate: The penicillin increases the effect and toxicity of methotrexate

Minocycline: Possible antagonism of action

Oxytetracycline: Possible antagonism of action

Rolitetracycline: Possible antagonism of action

Tetracycline: Possible antagonism of action

Thioridazine: Increased risk of cardiotoxicity and arrhythmias