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Identification
NameBenzylpenicillin
Accession NumberDB01053  (APRD00646)
Typesmall molecule
Groupsapproved
Description

Benzylpenicillin (Penicillin G) is narrow spectrum antibiotic used to treat infections caused by susceptible bacteria. It is a natural penicillin antibiotic that is administered intravenously or intramuscularly due to poor oral absorption. Penicillin G may also be used in some cases as prophylaxis against susceptible organisms.

Natural penicillins are considered the drugs of choice for several infections caused by susceptible gram positive aerobic organisms, such as Streptococcus pneumoniae, groups A, B, C and G streptococci, nonenterococcal group D streptococci, viridans group streptococci, and non-penicillinase producing staphylococcus. Aminoglycosides may be added for synergy against group B streptococcus (S. agalactiae), S. viridans, and Enterococcus faecalis. The natural penicillins may also be used as first or second line agents against susceptible gram positive aerobic bacilli such as Bacillus anthracis, Corynebacterium diphtheriae, and Erysipelothrix rhusiopathiae. Natural penicillins have limited activity against gram negative organisms; however, they may be used in some cases to treat infections caused by Neisseria meningitidis and Pasteurella. They are not generally used to treat anaerobic infections. Resistance patterns, susceptibility and treatment guidelines vary across regions.

Structure
Thumb
Synonyms
SynonymLanguageCode
6-(2-phenylacetamido)penicillanic acidNot AvailableNot Available
Benzylpenicillinic acidNot AvailableNot Available
PCGNot AvailableNot Available
Penicillin GNot AvailableNot Available
Salts
Name/CAS Structure Properties
Benzylpenicillin potassium
Thumb Not applicable DBSALT000981
Benzylpenicillin sodium
Thumb
  • InChI Key: FCPVYOBCFFNJFS-LQDWTQKMSA-M
  • Monoisotopic Mass: 356.080672407
  • Average Mass: 356.372
DBSALT000726
Brand names
NameCompany
PentidsNot Available
PfizerpenNot Available
Brand mixturesNot Available
Categories
CAS number61-33-6
WeightAverage: 334.39
Monoisotopic: 334.098727764
Chemical FormulaC16H18N2O4S
InChI KeyInChIKey=JGSARLDLIJGVTE-MBNYWOFBSA-N
InChI
InChI=1S/C16H18N2O4S/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/h3-7,11-12,14H,8H2,1-2H3,(H,17,19)(H,21,22)/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
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentPenicillins
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; Benzene and Substituted Derivatives; Tertiary Carboxylic Acid Amides; Thiazolidines; Tertiary Amines; Azetidines; Secondary Carboxylic Acid Amides; Hemiaminals; Thioethers; Carboxylic Acids; Enolates; Polyamines; Aminals
Substituentsn-acyl-alpha amino acid or derivative; benzene; tertiary carboxylic acid amide; thiazolidine; carboxamide group; tertiary amine; azetidine; hemiaminal; secondary carboxylic acid amide; aminal; polyamine; thioether; enolate; carboxylic acid derivative; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the penicillins. These are organic compounds containing the penicillin core structure, which is structurally characterized by a penam ring bearing two methyl groups at position 2, and an amide group at position 6 [starting from the sulfur atom at position 1].
Pharmacology
IndicationFor 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.
PharmacodynamicsPenicillin 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 actionBy 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.
AbsorptionRapidly 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.
Volume of distribution

0.53–0.67 L/kg in adults with normal renal function

Protein bindingBind to serum proteins (45-68%), mainly albumin.
Metabolism

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.

SubstrateEnzymesProduct
Benzylpenicillin
    6-aminopenicillanic acidDetails
    Benzylpenicillin
      Penicilloic acidDetails
      Route of eliminationPenicillin G is eliminated by the kidneys. Nonrenal clearance includes hepatic metabolism and, to a lesser extent, biliary excretion.
      Half lifeIn adults with normal renal function is reportedly 0.4–0.9 hours
      Clearance

      560ml/min in healthy humans

      ToxicityOral 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.
      Affected organisms
      • Enteric bacteria and other eubacteria
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption - 0.9059
      Blood Brain Barrier - 0.9954
      Caco-2 permeable - 0.8956
      P-glycoprotein substrate Substrate 0.6253
      P-glycoprotein inhibitor I Non-inhibitor 0.9374
      P-glycoprotein inhibitor II Non-inhibitor 0.9905
      Renal organic cation transporter Non-inhibitor 0.9485
      CYP450 2C9 substrate Non-substrate 0.7694
      CYP450 2D6 substrate Non-substrate 0.845
      CYP450 3A4 substrate Non-substrate 0.5133
      CYP450 1A2 substrate Non-inhibitor 0.9046
      CYP450 2C9 substrate Non-inhibitor 0.9187
      CYP450 2D6 substrate Non-inhibitor 0.9295
      CYP450 2C19 substrate Non-inhibitor 0.9026
      CYP450 3A4 substrate Non-inhibitor 0.8802
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.96
      Ames test Non AMES toxic 0.9193
      Carcinogenicity Non-carcinogens 0.6267
      Biodegradation Not ready biodegradable 0.989
      Rat acute toxicity 1.6523 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9993
      hERG inhibition (predictor II) Non-inhibitor 0.9223
      Pharmacoeconomics
      Manufacturers
      • King pharmaceuticals inc
      • Wyeth ayerst laboratories
      • Pfizer laboratories div pfizer inc
      • Teva pharmaceuticals usa inc
      • Mylan pharmaceuticals inc
      • Purepac pharmaceutical co
      • Apothecon sub bristol myers squibb co
      • Apothecon inc div bristol myers squibb
      • App pharmaceuticals llc
      • Consolidated pharmaceutical group inc
      • Gc hanford manufacturing co
      • Eli lilly and co
      • Marsam pharmaceuticals llc
      • Parke davis div warner lambert co
      • Sandoz inc
      • Baxter healthcare corp
      • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
      • Bristol myers squibb spa
      • John d copanos and co inc
      • Pharmacia and upjohn co
      Packagers
      Dosage forms
      FormRouteStrength
      Powder, for solutionIntramuscular
      Powder, for solutionIntravenous
      Powder, for solutionOral
      SuspensionOral
      TabletOral
      Prices
      Unit descriptionCostUnit
      Penicillin gk 20 million unit160.26USDeach
      Penicillin g na 5 million unit47.91USDeach
      Bicillin C-R (1200000) 2ml Syringe43.0USDsyringe
      Penicillin g k 5 million unit42.18USDeach
      Pfizerpen 20 million unit vial23.41USDvial
      Penicillin G Sodium 10000000 iu/vial9.35USDvial
      Pfizerpen 5 million unit vial7.99USDvial
      Penicillin G Sodium 5000000 iu/vial5.36USDvial
      Penicillin G Sodium 1000000 iu/vial2.52USDvial
      Pen g k 3 million unit/50 ml0.27USDml
      Pen g k 2 million unit/50 ml0.26USDml
      Pen g k 1 million unit/50 ml0.25USDml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point214-217 °CNot Available
      water solubilitySlightly soluble (210 mg/L)Not Available
      logP1.83HANSCH,C ET AL. (1995)
      pKa2.74 (at 25 °C)MERCK INDEX (1996)
      Predicted Properties
      PropertyValueSource
      water solubility2.85e-01 g/lALOGPS
      logP1.92ALOGPS
      logP1.08ChemAxon
      logS-3.1ALOGPS
      pKa (strongest acidic)3.53ChemAxon
      pKa (strongest basic)-2.6ChemAxon
      physiological charge-1ChemAxon
      hydrogen acceptor count4ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area86.71ChemAxon
      rotatable bond count4ChemAxon
      refractivity84.53ChemAxon
      polarizability33.54ChemAxon
      number of rings3ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Gunter Schumacher, Peter Buckel, “Plasmids for the increased production of penicillin G amidase.” U.S. Patent US5053335, issued May, 1984.

      US5053335
      General Reference
      1. Eagle H, Newman E, Musselman AD, Robinson M, Birmingham M: THE RENAL CLEARANCE OF PENICILLINS F, G, K, AND X IN RABBITS AND MAN. J Clin Invest. 1947 Sep;26(5):903-18. Pubmed
      External Links
      ResourceLink
      KEGG DrugD02336
      KEGG CompoundC05551
      PubChem Compound5904
      PubChem Substance46506778
      ChemSpider5693
      ChEBI18208
      ChEMBLCHEMBL29
      Therapeutic Targets DatabaseDNC001109
      PharmGKBPA450842
      HETPG1
      Drug Product Database712981
      RxListhttp://www.rxlist.com/cgi/generic3/pengk.htm
      ATC CodesJ01CE01S01AA14
      AHFS Codes
      • 08:12.16.04
      PDB EntriesNot Available
      FDA labelNot Available
      MSDSshow(47.7 KB)
      Interactions
      Drug Interactions
      Drug
      DemeclocyclinePossible antagonism of action
      DoxycyclinePossible antagonism of action
      MesoridazineIncreased risk of cardiotoxicity and arrhythmias
      MestranolThis anti-infectious agent could decreases the effect of the oral contraceptive
      MethacyclinePossible antagonism of action
      MethotrexateThe penicillin increases the effect and toxicity of methotrexate
      MinocyclinePossible antagonism of action
      OxytetracyclinePossible antagonism of action
      RolitetracyclinePossible antagonism of action
      TetracyclinePossible antagonism of action
      ThioridazineIncreased risk of cardiotoxicity and arrhythmias
      Food InteractionsNot Available

      1. Penicillin-binding protein 3

      Kind: protein

      Organism: Staphylococcus aureus (strain USA300)

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Penicillin-binding protein 3 Q2FGH1 Details

      References:

      1. Beise F, Labischinski H, Bradaczek H: On the relationships between molecular conformation, affinity towards penicillin-binding proteins, and biological activity of penicillin G-sulfoxide. Z Naturforsch C. 1988 Sep-Oct;43(9-10):656-64. Pubmed

      1. Solute carrier family 22 member 5

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 5 O76082 Details

      References:

      1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. Pubmed

      2. Solute carrier family 15 member 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 15 member 1 P46059 Details

      References:

      1. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed
      2. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. Pubmed

      3. Solute carrier family 15 member 2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 15 member 2 Q16348 Details

      References:

      1. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed

      4. Solute carrier family 22 member 6

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 6 Q4U2R8 Details

      References:

      1. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
      2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
      3. Hosoyamada M, Sekine T, Kanai Y, Endou H: Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Am J Physiol. 1999 Jan;276(1 Pt 2):F122-8. Pubmed
      4. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. Pubmed
      5. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
      6. Hasegawa M, Kusuhara H, Sugiyama D, Ito K, Ueda S, Endou H, Sugiyama Y: Functional involvement of rat organic anion transporter 3 (rOat3; Slc22a8) in the renal uptake of organic anions. J Pharmacol Exp Ther. 2002 Mar;300(3):746-53. Pubmed

      5. Solute carrier family 22 member 8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 8 Q8TCC7 Details

      References:

      1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
      2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. Pubmed
      3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
      4. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. Pubmed
      5. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed
      6. Hasegawa M, Kusuhara H, Sugiyama D, Ito K, Ueda S, Endou H, Sugiyama Y: Functional involvement of rat organic anion transporter 3 (rOat3; Slc22a8) in the renal uptake of organic anions. J Pharmacol Exp Ther. 2002 Mar;300(3):746-53. Pubmed
      7. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. Pubmed
      8. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. Pubmed

      6. Solute carrier family 22 member 4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 4 Q9H015 Details

      References:

      1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

      7. Solute carrier family 22 member 11

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 11 Q9NSA0 Details

      References:

      1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. Pubmed
      2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed

      8. Solute carrier organic anion transporter family member 2B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 2B1 O94956 Details

      References:

      1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. Pubmed

      9. Solute carrier organic anion transporter family member 4A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 4A1 Q96BD0 Details

      References:

      1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. Pubmed

      10. Solute carrier organic anion transporter family member 3A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 3A1 Q9UIG8 Details

      References:

      1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. Pubmed

      11. Solute carrier organic anion transporter family member 1B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

      References:

      1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on January 10, 2014 11:56