Procaine penicillin G

Absorption

After intramuscular injection, 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.

Toxicity

Procaine benzylpenicillin is associated with the pain at the injection site, blood clotting problems, and seizures. Treatment targeted against syphilis is often associated with Jarisch-Herxheimer reaction. The main unwanted effects are hypersensitivity reactions caused by the degradation products of penicillin, which combine with host protein and become antigenic. Other common adverse effects include skin rashes, fever and delayed serum sickness. Rare but fatal anaphylactic shock may occur. Oral LD50 values in mouse and rat are > 2000 mg/kg. Overdosage can cause convulsions, paralysis and even death. Emesis and gastric lavage may be of value if begun within a few hours of injection. Excessive blood concentrations can be lowered by haemodialysis .

Chemical properties

White, fine crystals or powder; odorless; relatively stable to air and light; solutions dextroro- tatory. Sparingly soluble in water; slightly soluble in alcohol; fairly soluble in chloroform.

Originator

Duracillin,Lilly,US,1948

The Uses of Procaine penicillin G

Antibacterial.

Indications

For the treatment of a number of bacterial infections such as syphilis, anthrax, mouth infections, pneumonia and diphtheria.

Background

Procaine benzylpenicillin (INN), also known as procaine G penicillin, is an injectable antiobiotic. It is a poorly soluble salt form of penicillin which is a combination of naturally occuring benzylpenicillin (penicillin G) and the local anaesthetic agent procaine in equimolar amounts. Procaine benzylpenicillin is administered by deep intramuscular injection. It is slowly absorbed and hydrolyzed to benzylpenicillin. This drug is used where prolonged exposure to benzylpenicillin at a low concentration is required. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin. It is widely used in veterinary settings. Benzylpenicillin is active against a wide range of organisms and is the drug of first choice for many infections.

Manufacturing Process

There was added to 250 ml of a concentrated butyl acetate extract containing 74,000 units of the acid form of penicillin per ml, 50 ml of a butyl acetate solution containing 0.238 g per ml of procaine base. The solution was agitated for one hour. The precipitate which formed was very gummy and not in the form of discrete crystals. This precipitate was crystallized by scratching the side of the vessel and agitating further. After this treatment 18.25 g of crystalline procaine penicillin was obtained which assayed 1010 units per mg representing a yield of 99.6% of the activity contained in the concentrated extract.

brand name

Duracillin(Lilly); Pfizerpen (Pfizer).

Therapeutic Function

Antibacterial

General Description

The first widely used amine salt of penicillin G wasmade with procaine. Penicillin G procaine (Crysticillin,Duracillin, Wycillin) can be made readily from penicillin Gsodium by treatment with procaine hydrochloride. This saltis considerably less soluble in water than the alkali metalsalts, requiring about 250 mL to dissolve 1 g. Free penicillinis released only as the compound dissolves and dissociates.It has an activity of 1,009 units/mg. A large number ofpreparations for injection of penicillin G procaine are commerciallyavailable. Most of these are either suspensions inwater to which a suitable dispersing or suspending agent, a buffer, and a preservative have been added or suspensions inpeanut oil or sesame oil that have been gelled by theaddition of 2% aluminum monostearate. Some commercialproducts are mixtures of penicillin G potassium or sodiumwith penicillin G procaine; the water-soluble salt providesrapid development of a high plasma concentration of penicillin,and the insoluble salt prolongs the duration of effect.

Pharmacokinetics

It is an antibiotic against penicillin-susceptible microorganisms with bactericidal effect. Like all penicillins, procaine benzylpenicillin interferes with the synthesis of the bacterial cell wall peptidoglycan. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable. It is part of the penicillin and beta lactam family of antibacterial drugs.

Safety Profile

Moderately toxic by intraperitoneal and intramuscular routes. Slightly toxic by ingestion and subcutaneous routes. When heated to decomposition it emits toxic vapors of NOx, and SOx.

Metabolism

Procaine is rapidly hydrolyzed by plasma esterases to nontoxic metabolites.