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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
1,5-Bis(4-amidinophenoxy)pentane
4,4'-(1,5-Pentanediylbis(oxy))bis-benzenecarboximidamide
4,4'-(Pentamethylenedioxy)dibenzamidine
4,4'-Diamidinodiphenoxypentane
P,P'-(pentamethylenedioxy)dibenzamidine
Pentamidin
Pentamidina
Pentamidindiisetionat
Pentamidine
Pentamidinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nebupentinhalant300 mg/6mLrespiratory (inhalation)APP Pharmaceuticals, LLC2011-02-15Not applicableUs
Pentacarinat 300 Inj Pws 300mg/vialpowder for solution300 mgintramuscular; inhalation; intravenousAventis Pharma Inc1989-12-312005-08-01Canada
Pentam 300injection, powder, lyophilized, for solution300 mg/3mLintramuscular; intravenousAPP Pharmaceuticals, LLC2001-01-16Not applicableUs
Pentamidine Isethionate Inj 300mg/vial BPpowder for solution300 mgintramuscular; intravenousDavid Bull Laboratories (Pty) Ltd.1990-12-311998-08-13Canada
Pentamidine Isetionate for Injection, BPpowder for solution300 mgintramuscular; intravenousHospira Healthcare Corporation1998-09-10Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PentacarinatSanofi-Aventis
PentacrinatAbbot
PentamAbbot
Pentamidine isethionateAbbot
PneumopentNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pentamidine Isethionate
ThumbNot applicableDBSALT000967
Categories
UNII673LC5J4LQ
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol ethers
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenol ether
  • Alkyl aryl ether
  • Carboximidamide
  • Ether
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.9416
Blood Brain Barrier+0.9133
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.5352
P-glycoprotein inhibitor INon-inhibitor0.8571
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.6653
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7339
CYP450 1A2 substrateNon-inhibitor0.5272
CYP450 2C9 inhibitorNon-inhibitor0.7439
CYP450 2D6 inhibitorNon-inhibitor0.7676
CYP450 2C19 inhibitorNon-inhibitor0.6581
CYP450 3A4 inhibitorNon-inhibitor0.8661
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5621
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8395
BiodegradationNot ready biodegradable0.9818
Rat acute toxicity2.2925 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7428
hERG inhibition (predictor II)Non-inhibitor0.7711
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Armour pharmaceutical co
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Inhalantrespiratory (inhalation)300 mg/6mL
Powder for solutionintramuscular; inhalation; intravenous300 mg
Injection, powder, lyophilized, for solutionintramuscular; intravenous300 mg/3mL
Powder for solutionintramuscular; intravenous300 mg
Prices
Unit descriptionCostUnit
Nebupent 300 mg inhal powder122.84USD each
Pentam 300 vial94.8USD vial
Pentamidine 300 mg vial45.31USD vial
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 Solubility0.0236 mg/mLALOGPS
logP1.32ALOGPS
logP2.32ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)12.13ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area118.2 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity120.53 m3·mol-1ChemAxon
Polarizability38.85 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  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:17191940 ]
External Links
ATC CodesP01CX01
AHFS Codes
  • 08:30.92
PDB Entries
FDA labelNot Available
MSDSDownload (50.6 KB)
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Pentamidine.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Pentamidine.
AlogliptinAlogliptin may increase the hypoglycemic activities of Pentamidine.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Pentamidine.
BortezomibThe metabolism of Pentamidine can be decreased when combined with Bortezomib.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Pentamidine.
ChlorpropamideChlorpropamide may increase the hypoglycemic activities of Pentamidine.
CitalopramPentamidine may increase the QTc-prolonging activities of Citalopram.
DabrafenibThe serum concentration of Pentamidine can be decreased when it is combined with Dabrafenib.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Pentamidine.
DofetilidePentamidine may increase the QTc-prolonging activities of Dofetilide.
FluvoxamineThe metabolism of Pentamidine can be decreased when combined with Fluvoxamine.
FoscarnetThe risk or severity of adverse effects can be increased when Pentamidine is combined with Foscarnet.
GliclazideGliclazide may increase the hypoglycemic activities of Pentamidine.
GlimepirideGlimepiride may increase the hypoglycemic activities of Pentamidine.
GliquidoneGliquidone may increase the hypoglycemic activities of Pentamidine.
GlyburideGlyburide may increase the hypoglycemic activities of Pentamidine.
GoserelinGoserelin may increase the QTc-prolonging activities of Pentamidine.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Pentamidine.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Pentamidine.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Pentamidine.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Pentamidine.
Insulin HumanInsulin Regular may increase the hypoglycemic activities of Pentamidine.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Pentamidine.
IvabradineIvabradine may increase the QTc-prolonging activities of Pentamidine.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Pentamidine.
LinagliptinLinagliptin may increase the hypoglycemic activities of Pentamidine.
LuliconazoleThe serum concentration of Pentamidine can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Pentamidine can be decreased when it is combined with Lumacaftor.
MequitazinePentamidine may increase the arrhythmogenic activities of Mequitazine.
MetforminMetformin may increase the hypoglycemic activities of Pentamidine.
MifepristoneMifepristone may increase the QTc-prolonging activities of Pentamidine.
OctreotideOctreotide may increase the QTc-prolonging activities of Pentamidine.
OxandroloneOxandrolone may increase the hypoglycemic activities of Pentamidine.
ParoxetineParoxetine may increase the hypoglycemic activities of Pentamidine.
PegvisomantPegvisomant may increase the hypoglycemic activities of Pentamidine.
PhenelzinePhenelzine may increase the hypoglycemic activities of Pentamidine.
PhenytoinThe metabolism of Pentamidine can be increased when combined with Phenytoin.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Pentamidine.
RepaglinideRepaglinide may increase the hypoglycemic activities of Pentamidine.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Pentamidine.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Pentamidine.
TestosteroneTestosterone may increase the hypoglycemic activities of Pentamidine.
TolbutamideTolbutamide may increase the hypoglycemic activities of Pentamidine.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Pentamidine.
VildagliptinVildagliptin may increase the hypoglycemic activities of Pentamidine.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
unknown
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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:17139284 ]
  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:17016423 ]
  3. Shankar SM, Nania JJ: Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. Paediatr Drugs. 2007;9(5):301-9. [PubMed:17927302 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other
General Function:
Trna methyltransferase activity
Specific Function:
Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).
Gene Name:
TRDMT1
Uniprot ID:
O14717
Molecular Weight:
44596.17 Da
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. doi: 10.1093/nar/gkm1180. Epub 2008 Feb 7. [PubMed:18263620 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Afrin LB, Afrin JB: Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration. Clin Transplant. 2011 May-Jun;25(3):E271-5. doi: 10.1111/j.1399-0012.2011.01399.x. Epub 2011 Feb 7. [PubMed:21299635 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
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:12920490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  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:12920490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
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:12920490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Leukotriene-b4 20-monooxygenase activity
Specific Function:
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).
Gene Name:
CYP4A11
Uniprot ID:
Q02928
Molecular Weight:
59347.31 Da
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:12920490 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23