Identification

Name
Pentetic acid
Accession Number
DB14007
Description

Pentetic acid, also known as diethylenetriaminepentaacetic acid (DTPA), is a synthetic polyamino carboxylic acid with eight coordinate bond forming sites that can sequester metal ions and form highly stable DTPA-metal ion complexes. DTPA, along with its calcium and zinc trisodium salts, are the only FDA approved agents for the treatment of internal contamination by transuranics.1 It is currently considered, in all the dosage forms, as a member of the list of approved inactive ingredients for drug products by the FDA.6 DPTA was developed by the pharmaceutical company CIS US and FDA approved on April 14, 2004.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 393.349
Monoisotopic: 393.138343953
Chemical Formula
C14H23N3O10
Synonyms
  • Diethylene triamine pentaacetic acid
  • Diethylenetriamine pentaacetic acid
  • Diethylenetriaminepentaacetate
  • Diethylenetriaminepentaacetic acid
  • DTP-A
  • DTPA
  • Pentetate
  • Pentetic acid

Pharmacology

Indication

DTPA is widely used in industry and medicine. As a medical agent, it is approved for its use in medical imaging and for the decorporation of internally deposited radionuclides.1 It is FDA approved for the treatment of individuals with known or suspected internal contamination with plutonium, americium or curium to increase the rates of elimination.7

Due to the pharmacokinetic elimination by the kidneys, pentetic acid conjugated with technetium Tc-99m is being used clinically to estimate physiological parameters such as glomerular filtration rat and effective renal plasma flow.4

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

There are reports in vivo of low stability of complexes of DPTA with uranium and neptunium which is being reported to cause deposition of the radionuclides into the tissues.5 In the case of plutonium, some preclinical studies have shown a very high urine elimination efficacy 1 hour after initial contamination. This efficacy is conserved for approximately 24 hours while the radiocontaminant is circulating. When the radionuclide is inhaled, it has been reported a DPTA-induced reduction of even 98% of the lung deposits. It is important to consider that pentetic acid can bind directly to other trace metals in the body which can cause deficiencies.3

Mechanism of action

The calcium and zinc trisodium salts of DTPA achieve the therapeutical potential by exchanging calcium and zinc cations with transuranic radionuclides to form higher affinity complexes and then promote their elimination by glomerular filtration into the urine. DTPA as an acid acts in a very similar way by sequestering ions with its eight coordinate bond forming sites.1

TargetActionsOrganism
ATransuranium elements
chelator
Humans
Absorption

DTPA and its trisodium salts present a very poor bioavailability after oral administration. Therefore, the normal administration of DTPA is done by slow intravenous infusion or inhalation with a nebulizer.1 When inhaled, the absorption is of about 20% of the administered dose.3

Volume of distribution

The volume of distribution of DPTA is 17 L.4

Protein binding

The fast clearance and very short half-life of pentetic acid suggest that this compound is very unlikely to become bound to serum proteins to any significant extent.2 It is reported that DPTA is negligibly bound to alpha1-antitrypsin.4

Metabolism

Pentetic acid and its derivatives present a very minimal metabolism in the body.3

Route of elimination

DTPA metal complexes are quickly excreted in the urine.7It is predominantly excreted by the kidney and it is not excreted by non-renal routes to any significant extent.4

Half-life

In preclinical studies, DTPA has been shown to present a very short half-life of 18.5-31.8 min after intravenous administration.

Clearance

Pentetic acid presents a very rapid blood clearance which explains for the short half-life.2 The reported clearance rate in patients with normal renal function is 80-120ml/min.4

Adverse Effects
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Toxicity

Some toxicity has been reported related to administration of pentetic acid including depletion of trace metals, kidney and liver vacuolization and small bowel hemorrhage lesions.2

Affected organisms
  • Humans and other mammals
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
AbacavirAbacavir may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Pentetic acid which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Pentetic acid 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
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pentetate calcium trisodiumG79YN26H5B12111-24-9AYFCVLSUPGCQKD-UHFFFAOYSA-I
Pentetate zinc trisodiumNXU65IC8PG11082-38-5HVASDHJNLYRZEA-UHFFFAOYSA-I
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Draximage DtpaInjection, powder, lyophilized, for solution20 mg/1Intravenous; Respiratory (inhalation)Jubilant DraxImage Inc., dba Jubilant Radiopharma1989-12-29Not applicableUS flag
Kit for the Preparation of Technetium Tc 99m Pentetate InjectionInjection20.6 mg/10mLIntravenousPharmalucence, Inc.1976-11-162010-08-02US flag
Pentetate calcium trisodiumInjection, solution, concentrate1000 mg/5mLIntravenous; Respiratory (inhalation)Hameln Pharma Plus Gmbh2004-08-11Not applicableUS flag
Pentetate Calcium TrisodiumInjection, solution, concentrate200 mg/1mLIntravenous; Respiratory (inhalation)Hameln Pharmaceuticals2006-12-18Not applicableUS flag
Pentetate Zinc TrisodiumInjection, solution, concentrate200 mg/1mLIntravenous; Respiratory (inhalation)Hameln Pharmaceuticals2006-12-18Not applicableUS flag
Pentetate zinc trisodiumInjection, solution, concentrate1000 mg/5mLIntravenous; Respiratory (inhalation)Hameln Pharma Plus Gmbh2004-08-11Not applicableUS flag
Pentetic AcidInjection20 mg/1IntravenousJubilant HollisterStier General Partnership1989-12-29Not 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

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pentacarboxylic acids and derivatives. These are carboxylic acids containing exactly five carboxyl groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Pentacarboxylic acids and derivatives
Direct Parent
Pentacarboxylic acids and derivatives
Alternative Parents
Alpha amino acids / Trialkylamines / Amino acids / Carboxylic acids / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aliphatic acyclic compound / Alpha-amino acid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Carbonyl group / Carboxylic acid / Hydrocarbon derivative / Organic nitrogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
pentacarboxylic acid (CHEBI:35739)

Chemical Identifiers

UNII
7A314HQM0I
CAS number
67-43-6
InChI Key
QPCDCPDFJACHGM-UHFFFAOYSA-N
InChI
InChI=1S/C14H23N3O10/c18-10(19)5-15(1-3-16(6-11(20)21)7-12(22)23)2-4-17(8-13(24)25)9-14(26)27/h1-9H2,(H,18,19)(H,20,21)(H,22,23)(H,24,25)(H,26,27)
IUPAC Name
2-[bis({2-[bis(carboxymethyl)amino]ethyl})amino]acetic acid
SMILES
OC(=O)CN(CCN(CC(O)=O)CC(O)=O)CCN(CC(O)=O)CC(O)=O

References

General References
  1. Yang YT, Di Pasqua AJ, Zhang Y, Sueda K, Jay M: Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): formulation design and optimization studies. Pharm Dev Technol. 2014 Nov;19(7):806-12. doi: 10.3109/10837450.2013.836216. Epub 2013 Sep 19. [PubMed:24047113]
  2. Harrington KJ, Rowlinson-Busza G, Syrigos KN, Uster PS, Abra RM, Stewart JS: Biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies. Br J Cancer. 2000 Jul;83(2):232-8. doi: 10.1054/bjoc.1999.1232. [PubMed:10901376]
  3. Abe T: [Pharmacological properties and clinical efficacy of pentetate calcium trisodium and pentetate zinc trisodium, antidotes for transuranium elements]. Nihon Yakurigaku Zasshi. 2012 Jan;139(1):33-8. [PubMed:22230879]
  4. Reilly R. (2013). The fundamental principles of compartmental pharmacokinetics illustrated by radiopharmaceuticals commonly used in nuclear medicine. ACPE.
  5. Zhou H. and Theil F. (2016). ADME amd translational pharmacokinetics/pharmacodynamics of therapeutic proteins. John Wiley & Sons.
  6. FDA Inactive ingredient search [Link]
  7. FDA guidelines [Link]
  8. FDA orphan list [Link]
ChemSpider
2945
RxNav
3690
ChEBI
35739
ChEMBL
CHEMBL780
ZINC
ZINC000019419017
Wikipedia
Pentetate
FDA label
Download (204 KB)
MSDS
Download (232 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionAcellular Pertussis / Diphtheria / Diphtheria-Tetanus-aPertussis-Poliomyelitis Vaccines / Haemophilus Influenzae Type B / Poliomyelitis / Tetanus1
4CompletedPreventionAcellular Pertussis / Diphtheria / Haemophilus Influenzae Type B / Poliomyelitis / Tetanus / Viral Hepatitis B2
4CompletedPreventionAcellular Pertussis / Diphtheria / Tetanus2
4Not Yet RecruitingPreventionDiphtheria1
4RecruitingScreeningHepatocellular Carcinoma / Liver Cancer / Liver Cirrhoses1
3CompletedPreventionAcellular Pertussis / Diphtheria / Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines / Haemophilus Influenzae Type B / Poliomyelitis / Tetanus / Viral Hepatitis B1
3CompletedPreventionAcellular Pertussis / Diphtheria / Haemophilus Influenzae Type B / Poliomyelitis / Tetanus1
3CompletedPreventionAcellular Pertussis / Diphtheria / Haemophilus Influenzae Type B / Poliomyelitis / Tetanus / Viral Hepatitis B2
3CompletedPreventionAcellular Pertussis / Diphtheria / Haemophilus Influenzae Type B / Tetanus1
3CompletedPreventionAcellular Pertussis / Diphtheria / Poliomyelitis / Streptococcus Pneumoniae Vaccines / Tetanus / Viral Hepatitis B1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous; Respiratory (inhalation)20 mg/1
InjectionIntravenous20.6 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous7.8 mg
Injection, powder, lyophilized, for solutionIntravenous; Oral; Respiratory (inhalation)9.1 mg
Injection, solution, concentrateIntravenous; Respiratory (inhalation)1000 mg/5mL
Injection, solution, concentrateIntravenous; Respiratory (inhalation)200 mg/1mL
InjectionIntravenous20 mg/1
Injection, powder, lyophilized, for solutionIntravenous10 mg
Injection, powder, lyophilized, for solutionIntravenous20.8 mg
InjectionIntravenous20.8 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)219-220 ºCZhang, et al. AAPS J. (2013)
boiling point (°C)Decomposes'MSDS'
water solubilityHighly solubleZhang, et al. AAPS J. (2013)
logP-4.90Zhang, et al. AAPS J. (2013)
pKapentabasic (1.5-10.6)BASF techinical information
Predicted Properties
PropertyValueSource
Water Solubility4.18 mg/mLALOGPS
logP-1.3ALOGPS
logP-6.3ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.95ChemAxon
pKa (Strongest Basic)8.82ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area196.22 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity86.45 m3·mol-1ChemAxon
Polarizability36.41 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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

Targets

1. Transuranium elements
Kind
Group
Organism
Humans
Pharmacological action
Yes
Actions
Chelator
Plutonium, americium or curium
References
  1. Yang YT, Di Pasqua AJ, Zhang Y, Sueda K, Jay M: Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): formulation design and optimization studies. Pharm Dev Technol. 2014 Nov;19(7):806-12. doi: 10.3109/10837450.2013.836216. Epub 2013 Sep 19. [PubMed:24047113]
  2. FDA guidelines [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. T...
Gene Name
SERPINA1
Uniprot ID
P01009
Uniprot Name
Alpha-1-antitrypsin
Molecular Weight
46736.195 Da
References
  1. Reilly R. (2013). The fundamental principles of compartmental pharmacokinetics illustrated by radiopharmaceuticals commonly used in nuclear medicine. ACPE.

Drug created on April 10, 2018 10:42 / Updated on June 12, 2020 10:53

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