Procaine benzylpenicillin

Identification

Name
Procaine benzylpenicillin
Accession Number
DB09320
Type
Small Molecule
Groups
Approved, Vet approved
Description

Procaine benzylpenicillin (INN), also known as procaine G penicillin, is an antibiotic useful for the treatment of a number of bacterial infections. 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. Following deep intramuscular injection, it is slowly absorbed into the circulation and hydrolysed to benzylpenicillin — thus it is used where prolonged low concentrations of benzylpenicillin are 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.

Structure
Thumb
Synonyms
  • Penicillin G procaine
Active Moieties
NameKindUNIICASInChI Key
Procaineunknown4Z8Y51M43859-46-1MFDFERRIHVXMIY-UHFFFAOYSA-N
BenzylpenicillinunknownQ42T66VG0C61-33-6JGSARLDLIJGVTE-MBNYWOFBSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ayercillin SuspensionSuspension300000 unitIntramuscularAyerst Laboratories1951-12-311999-04-12Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Penicillin G ProcaineInjection, suspension1200000 [iU]/2mLIntramuscularPfizer Laboratories Div Pfizer Inc.1948-04-26Not applicableUs
Penicillin G ProcaineInjection600000 [iU]/1mLIntramuscularMonarch Pharmaceuticals,Inc.1948-04-262007-09-14Us
Penicillin G ProcaineInjection, suspension600000 [iU]/1mLIntramuscularPfizer Laboratories Div Pfizer Inc.1948-04-26Not applicableUs
Penicillin G ProcaineInjection1200000 [iU]/2mLIntramuscularMonarch Pharmaceuticals,Inc.1948-04-262007-09-14Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Bicillin A-P Injection PwsProcaine benzylpenicillin (300000 unit) + Benzylpenicillin benzathine hydrate (600000 unit) + Benzylpenicillin potassium (300000 unit)Powder, for solutionIntramuscularWyeth Ayerst Canada Inc.1995-12-311996-09-10Canada
Bicillin C-R 900/300Procaine benzylpenicillin (300000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (900000 [iU]/2mL)Injection, suspensionIntramuscularPfizer Laboratories Div Pfizer Inc.1953-05-18Not applicableUs
Bicillin CRProcaine benzylpenicillin (600000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (600000 [iU]/2mL)Injection, suspensionIntramuscularA-S Medication Solutions1953-05-18Not applicableUs
Bicillin CRProcaine benzylpenicillin (600000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (600000 [iU]/2mL)Injection, suspensionIntramuscularPfizer Laboratories Div Pfizer Inc.1953-05-18Not applicableUs
Bicillin CRProcaine benzylpenicillin (600000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (600000 [iU]/2mL)Injection, suspensionIntramuscularDispensing Solutions, Inc.1953-05-18Not applicableUs
Bicillin CRProcaine benzylpenicillin (600000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (600000 [iU]/2mL)Injection, suspensionIntramuscularPhysicians Total Care, Inc.2008-08-28Not applicableUs
Bicillin CRProcaine benzylpenicillin (600000 [iU]/2mL) + Benzylpenicillin benzathine hydrate (600000 [iU]/2mL)Injection, suspensionIntramuscularPfizer Laboratories Div Pfizer Inc.1953-05-18Not applicableUs
Categories
UNII
1LW5K9CIR1
CAS number
54-35-3
Weight
Average: 570.71
Monoisotopic: 570.251206134
Chemical Formula
C29H38N4O6S
InChI Key
WHRVRSCEWKLAHX-LQDWTQKMSA-N
InChI
InChI=1S/C16H18N2O4S.C13H20N2O2/c1-16(2)12(15(21)22)18-13(20)11(14(18)23-16)17-10(19)8-9-6-4-3-5-7-9;1-3-15(4-2)9-10-17-13(16)11-5-7-12(14)8-6-11/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22);5-8H,3-4,9-10,14H2,1-2H3/t11-,12+,14-;/m1./s1
IUPAC Name
(2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 2-(diethylamino)ethyl 4-aminobenzoate
SMILES
CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1)C(O)=O

Pharmacology

Indication

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

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

Procaine benzylpenicillin is hydrolyzed into penicillin G once it is released from the injection site. Penicillin G attaches to the penicillin-binding proteins on bacterial cell wall and inhibit the transpeptidation enzyme that crosslinks the peptide chains attached to the backbone of the peptidoglycan. The final bactericidal event involves the inactivation of an inhibitor of autolytic enzymes in the cell wall, leading to lysis of the bacterium [4].

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.

Volume of distribution

The drug is distributed throughout the body tissues in widely varying amounts and spinal fluid to a lesser degree. Highest levels are found in the kidneys with lesser amounts in the liver, skin, and intestines. It displays low solubility thus results in blood serum levels much lower but more prolonged than other parenteral penicillins.

Protein binding

Approximately 60% of penicillin G is bound to serum protein.

Metabolism

Procaine is rapidly hydrolyzed by plasma esterases to nontoxic metabolites.

Route of elimination

The drug is rapidly and predominantly cleared via renal elimination, with 90% being through tubular secretion. Approximately 60 -90 % of a dose of parenteral penicillin G is excreted in the urine within 24 to 36 hours.

Half life

Intramuscular injection of benzylpenicillin has a plasma half-life of 30 minutes [6].

Clearance
Not Available
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 [6].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcemetacinAcemetacin may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
AcenocoumarolProcaine benzylpenicillin may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Procaine benzylpenicillin.
AmilorideAmiloride may increase the excretion rate of Procaine benzylpenicillin which could result in a lower serum level and potentially a reduction in efficacy.
AmlodipineAmlodipine may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
AmphetamineAmphetamine may decrease the excretion rate of Procaine benzylpenicillin which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Olsen L, Ingvast-Larsson C, Brostrom H, Larsson P, Tjalve H: Clinical signs and etiology of adverse reactions to procaine benzylpenicillin and sodium/potassium benzylpenicillin in horses. J Vet Pharmacol Ther. 2007 Jun;30(3):201-7. [PubMed:17472651]
  2. Uboh CE, Soma LR, Luo Y, McNamara E, Fennell MA, May L, Teleis DC, Rudy JA, Watson AO: Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses. Am J Vet Res. 2000 Jul;61(7):811-5. [PubMed:10895905]
  3. Papich MG, Korsrud GO, Boison JO, Yates WD, MacNeil JD, Janzen ED, McKinnon JJ, Landry DA: Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle. Am J Vet Res. 1994 Jun;55(6):825-30. [PubMed:7944023]
  4. 51. (2016). In Rang & Dale's pharmacology (8th ed., pp. 626-641). Elsevier Churchill Livingstone. [ISBN:978-0-7020-5362-7]
  5. product info [Link]
  6. World Health Organization Model Prescribing Information: Drugs Used in Skin Diseases [Link]
External Links
PubChem Compound
5903
PubChem Substance
310265202
ChemSpider
5692
ChEBI
52154
ChEMBL
CHEMBL1628385
Wikipedia
Procaine_benzylpenicillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CE09 — Procaine benzylpenicillin
FDA label
Download (658 KB)
MSDS
Download (44.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SuspensionIntramuscular300000 unit
Powder, for solutionIntramuscular
Injection, suspensionIntramuscular
InjectionIntramuscular1200000 [iU]/2mL
InjectionIntramuscular600000 [iU]/1mL
Injection, suspensionIntramuscular1200000 [iU]/2mL
Injection, suspensionIntramuscular600000 [iU]/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.285 mg/mLALOGPS
logP1.92ALOGPS
logP1.08ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.53ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.71 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity84.53 m3·mol-1ChemAxon
Polarizability33.5 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Penicillins / N-acyl-alpha amino acids and derivatives / Phenylacetamides / Thiazolidines / Tertiary carboxylic acid amides / Azetidines / Secondary carboxylic acid amides / Azacyclic compounds / Thiohemiaminal derivatives / Carboxylic acids
show 7 more
Substituents
Alpha-dipeptide / Penicillin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Phenylacetamide / Penam / Monocyclic benzene moiety / Benzenoid / Beta-lactam / Thiazolidine
show 21 more
Molecular Framework
Not Available
External Descriptors
procaine(1+) salt (CHEBI:52154)

Drug created on November 17, 2015 10:30 / Updated on September 07, 2018 03:25