Identification

Name
Pentamidine
Accession Number
DB00738
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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 340.4195
Monoisotopic: 340.189926032
Chemical Formula
C19H24N4O2
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
  • Pentamidine
  • Pentamidinum
External IDs
  • MB 800
  • RP 2512

Pharmacology

Indication

For the treatment of pneumonia due to Pneumocystis carinii.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pentamidine 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 action

The 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.

TargetActionsOrganism
UDNA
intercalation
Humans
UtRNA (cytosine(38)-C(5))-methyltransferase
other
Humans
Absorption

Absorbed poorly through the gastrointestinal tract and is usually administered parenterally.

Volume of distribution
Not Available
Protein binding

69%

Metabolism

Hepatic.

Route of elimination
Not Available
Half-life

9.1-13.2 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Symptoms of overdose include pain, nausea, anorexia, hypotension, fever, rash, bad taste in mouth, confusion/hallucinations, dizziness, and diarrhea.

Affected organisms
  • Pneumocystis carinii
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirPentamidine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Pentamidine can be increased when combined with Abatacept.
AbirateroneThe metabolism of Pentamidine can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Pentamidine can be decreased when combined with Acalabrutinib.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Pentamidine.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Pentamidine.
AceclofenacPentamidine may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Pentamidine is combined with Acemetacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Pentamidine.
AcetaminophenPentamidine may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pentamidine gluconateB0WU872RIR123245-08-9JAVCHNFPSHBZAF-UUPCJSQJSA-N
Pentamidine isethionateV2P3K60DA2140-64-7YBVNFKZSMZGRAD-UHFFFAOYSA-N
Pentamidine mesylate863QBB4D0A6823-79-6WRXSODAXJSKMAW-UHFFFAOYSA-N
International/Other Brands
Pentacarinat (Sanofi-Aventis) / Pentacrinat (Abbot) / Pentam (Abbot) / Pneumopent
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NebuPentInhalant300 mg/6mLRespiratory (inhalation)Physicians Total Care, Inc.1994-06-092010-06-30US flag
NebuPentInhalant300 mg/6mLRespiratory (inhalation)Fresenius Kabi USA, LLC2011-02-15Not applicableUS flag
Pentacarinat 300 Inj Pws 300mg/vialPowder, for solutionIntramuscular; Intravenous; Respiratory (inhalation)Aventis Pharma Ltd.1989-12-312005-08-01Canada flag
Pentam 300Injection, powder, lyophilized, for solution300 mg/3mLIntramuscular; IntravenousFresenius Kabi USA, LLC2001-01-16Not applicableUS flag
Pentamidine Isethionate Inj 300mg/vial BPPowder, for solutionIntramuscular; IntravenousDavid Bull Laboratories (Pty) Ltd.1990-12-311998-08-13Canada flag
Pentamidine Isetionate for Injection BPPowder, for solutionIntramuscular; IntravenousPfizer Canada Ulc1998-09-10Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Pentamidine IsethionateInjection, powder, lyophilized, for solution300 mg/300mgIntramuscular; IntravenousSeton Pharmaceuticals2018-04-01Not applicableUS flag
Pentamidine IsethionateInhalant300 mg/300mgRespiratory (inhalation)Seton Pharmaceuticals2019-10-14Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
P01CX01 — Pentamidine isethionate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Alkyl aryl ethers / Carboximidamides / Carboxamidines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Alkyl aryl ether / Amidine / Aromatic homomonocyclic compound / Carboximidamide / Carboxylic acid amidine / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carboxamidine, diether (CHEBI:45081)

Chemical Identifiers

UNII
673LC5J4LQ
CAS number
100-33-4
InChI Key
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

References

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]
Human Metabolome Database
HMDB0014876
KEGG Compound
C07420
PubChem Compound
4735
PubChem Substance
46508562
ChemSpider
4573
BindingDB
45440
RxNav
7994
ChEBI
45081
ChEMBL
CHEMBL55
ZINC
ZINC000001530775
Therapeutic Targets Database
DAP000764
PharmGKB
PA450850
PDBe Ligand
PNT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pentamidine
AHFS Codes
  • 08:30.92 — Miscellaneous Antiprotozoals
PDB Entries
1d64 / 1rkw / 3cr4 / 3cr5 / 3ey0 / 3gy3 / 3hii
MSDS
Download (50.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4WithdrawnTreatmentPneumocystis Jirovecii Pneumonia1
3CompletedPreventionHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Visceral Leishmaniosis1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumocystis Jirovecii Pneumonia6
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumocystis Jirovecii Pneumonia1
2CompletedTreatmentCutaneous Leishmaniases1
2CompletedTreatmentDiabetes Mellitus, Insulin-Dependent1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumocystis Jirovecii Pneumonia1
2CompletedTreatmentLeishmaniasis, Cutaneous1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1

Pharmacoeconomics

Manufacturers
  • App pharmaceuticals llc
  • Armour pharmaceutical co
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Watson laboratories inc
Packagers
  • APP Pharmaceuticals
  • APPD
  • Baxter International Inc.
  • Hospira Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection
InhalantRespiratory (inhalation)300 mg/6mL
Injection, powder, for solution300 mg
Injection, powder, for solutionParenteral300 MG
Injection, powder, for solutionIntramuscular; Intravenous; Respiratory (inhalation)300 mg
Powder, for solutionIntramuscular; Intravenous; Respiratory (inhalation)
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous300 mg/3mL
InhalantRespiratory (inhalation)300 mg/300mg
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous300 mg/300mg
Powder, for solutionIntramuscular; Intravenous
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)186.0 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-e30f537a55b02f867429
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-18ffa88d8e83e0c224b3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0309000000-22a206e2fffa6ce5cf2f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dr-0900000000-d135e9c44dbf5da10735
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-d01e29cdf614c3660180
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-0009000000-1499530d0d768e480fd7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-0009000000-3c60569ced478a95001f
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0209000000-58a168dde59140860009
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00dr-0901000000-7cd36861b140e4e5a6a2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0900000000-60dfcd75868e869bcbf7
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-00di-0009000000-6677c6c06aa266d05ff1

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Unknown
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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
Humans
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
Uniprot Name
tRNA (cytosine(38)-C(5))-methyltransferase
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
Humans
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
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
Humans
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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
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
Humans
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 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]
  2. Kip AE, Schellens JHM, Beijnen JH, Dorlo TPC: Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs. Clin Pharmacokinet. 2018 Feb;57(2):151-176. doi: 10.1007/s40262-017-0570-0. [PubMed:28756612]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
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
Humans
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 2...
Gene Name
CYP4A11
Uniprot ID
Q02928
Uniprot Name
Cytochrome P450 4A11
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]

Drug created on June 13, 2005 07:24 / Updated on October 29, 2020 19:25

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