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Identification
NamePentamidine
Accession NumberDB00738  (APRD00303, EXPT02625)
Typesmall molecule
Groupsapproved
Description

Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of pneumocystis pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
PentamidinGermanINN
PentamidinaSpanishINN
PentamidindiisetionatNot AvailablePH: Ph. Eur. 7
PentamidineFrenchINN
PentamidinumLatinINN
Salts
Name/CAS Structure Properties
Pentamidine Isethionate
Thumb Not applicable DBSALT000967
Brand names
NameCompany
NebuPentAPP
PentacarinatSanofi-Aventis
PentacrinatAbbot
PentamAbbot
Pentam 300Abbot
Pentamidine isethionateAbbot
PneumopentNot Available
Brand mixturesNot Available
Categories
CAS number100-33-4
WeightAverage: 340.4195
Monoisotopic: 340.189926032
Chemical FormulaC19H24N4O2
InChI KeyInChIKey=XDRYMKDFEDOLFX-UHFFFAOYSA-N
InChI
InChI=1S/C19H24N4O2/c20-18(21)14-4-8-16(9-5-14)24-12-2-1-3-13-25-17-10-6-15(7-11-17)19(22)23/h4-11H,1-3,12-13H2,(H3,20,21)(H3,22,23)
IUPAC Name
4-{[5-(4-carbamimidoylphenoxy)pentyl]oxy}benzene-1-carboximidamide
SMILES
NC(=N)C1=CC=C(OCCCCCOC2=CC=C(C=C2)C(N)=N)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenol Ethers
Direct parentPhenol Ethers
Alternative parentsAlkyl Aryl Ethers; Carboxamidines; Polyamines
Substituentsalkyl aryl ether; ether; polyamine; amidine; carboxylic acid amidine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Pharmacology
IndicationFor the treatment of pneumonia due to Pneumocystis carinii.
PharmacodynamicsPentamidine is an antiprotozoal agent. It is an aromatic diamidine, and is known to have activity against Pneumocystis carinii. The exact nature of its antiprotozoal action is unknown. in vitro studies with mammalian tissues and the protozoan Crithidia oncopelti indicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. The medication is also useful in Leishmaniasis and in prophylaxis against sleeping sickness caused by Trypanosoma brucei gambiense. Hydration before treatment lessens the incidence and severity of side effects, which include liver or kidney dysfunction, hypertension, hypotension, hypoglycemia, hypocalemia, leukopenia, thrombcytopenia, anemia, and allergic reaction. It is generally well-tolerated.
Mechanism of actionThe mode of action of pentamidine is not fully understood. It is thought that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids, and proteins.
AbsorptionAbsorbed poorly through the gastrointestinal tract and is usually administered parenterally.
Volume of distributionNot Available
Protein binding69%
Metabolism

Hepatic.

Route of eliminationNot Available
Half life9.1-13.2 hours
ClearanceNot Available
ToxicitySymptoms of overdose include pain, nausea, anorexia, hypotension, fever, rash, bad taste in mouth, confusion/hallucinations, dizziness, and diarrhea.
Affected organisms
  • Pneumocystis carinii
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9416
Blood Brain Barrier + 0.9133
Caco-2 permeable - 0.8957
P-glycoprotein substrate Non-substrate 0.5352
P-glycoprotein inhibitor I Non-inhibitor 0.8571
P-glycoprotein inhibitor II Non-inhibitor 0.8382
Renal organic cation transporter Inhibitor 0.6653
CYP450 2C9 substrate Non-substrate 0.7898
CYP450 2D6 substrate Non-substrate 0.9115
CYP450 3A4 substrate Non-substrate 0.7339
CYP450 1A2 substrate Non-inhibitor 0.5272
CYP450 2C9 substrate Non-inhibitor 0.7439
CYP450 2D6 substrate Non-inhibitor 0.7676
CYP450 2C19 substrate Non-inhibitor 0.6581
CYP450 3A4 substrate Non-inhibitor 0.8661
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5621
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.8395
Biodegradation Not ready biodegradable 0.9818
Rat acute toxicity 2.2925 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7428
hERG inhibition (predictor II) Non-inhibitor 0.7711
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Armour pharmaceutical co
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Nebupent 300 mg inhal powder122.84USDeach
Pentam 300 vial94.8USDvial
Pentamidine 300 mg vial45.31USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point186.0 °C (decomposes)Not Available
water solubilityCompleteNot Available
logP4Not Available
Predicted Properties
PropertyValueSource
water solubility2.36e-02 g/lALOGPS
logP1.32ALOGPS
logP2.32ChemAxon
logS-4.2ALOGPS
pKa (strongest basic)12.13ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count6ChemAxon
hydrogen donor count4ChemAxon
polar surface area118.2ChemAxon
rotatable bond count10ChemAxon
refractivity120.53ChemAxon
polarizability38.85ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Nguewa PA, Fuertes MA, Cepeda V, Iborra S, Carrion J, Valladares B, Alonso C, Perez JM: Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem Biodivers. 2005 Oct;2(10):1387-400. Pubmed
External Links
ResourceLink
KEGG CompoundC07420
PubChem Compound4735
PubChem Substance46508562
ChemSpider4573
ChEBI45081
ChEMBLCHEMBL55
Therapeutic Targets DatabaseDAP000764
PharmGKBPA450850
HETPNT
Drug Product Database2183080
RxListhttp://www.rxlist.com/cgi/generic3/pentam.htm
Drugs.comhttp://www.drugs.com/cdi/pentamidine.html
WikipediaPentamidine
ATC CodesP01CX01
AHFS Codes
  • 08:30.92
PDB Entries
FDA labelNot Available
MSDSshow(50.6 KB)
Interactions
Drug Interactions
Drug
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
QuinupristinThis combination presents an increased risk of toxicity
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TelavancinAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
TiclopidineTiclopidine may decrease the metabolism and clearance of Pentamidine. Consider alternate therapy or monitor for adverse/toxic effects of Pentamidine if Ticlopidine is initiated, discontinued or dose changed.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZalcitabineAdditive risk of pancreatitis. Concomitant therapy should be avoided.
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol decanoateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food InteractionsNot Available

1. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: unknown

Actions: intercalation

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Shankar SM, Nania JJ: Management of Pneumocystis jiroveci Pneumonia in Children Receiving Chemotherapy. Paediatr Drugs. 2007;9(5):301-9. Pubmed

2. tRNA (cytosine(38)-C(5))-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other

Components

Name UniProt ID Details
tRNA (cytosine(38)-C(5))-methyltransferase O14717 Details

References:

  1. Sun T, Zhang Y: Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation. Nucleic Acids Res. 2008 Mar;36(5):1654-64. Epub 2008 Feb 7. Pubmed

1. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Afrin LB, Afrin JB: Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration. Clin Transplant. 2011 Feb 7. doi: 10.1111/j.1399-0012.2011.01399.×. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. Pubmed

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. Pubmed

4. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. Pubmed

5. Cytochrome P450 4A11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 4A11 Q02928 Details

References:

  1. Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM: Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42. Epub 2003 Aug 12. Pubmed

6. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11