Identification

Name
Pentetic acid
Accession Number
DB14007  (DB11322, DBSALT001589)
Type
Small Molecule
Groups
Approved
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]

Structure
Thumb
Synonyms
  • Diethylene triamine pentaacetic acid
  • Diethylenetriamine pentaacetic acid
  • Diethylenetriaminepentaacetate
  • Diethylenetriaminepentaacetic acid
  • DTP-A
  • DTPA
  • Pentetate
Product Ingredients
IngredientUNIICASInChI Key
Pentetate calcium trisodiumG79YN26H5B12111-24-9AYFCVLSUPGCQKD-UHFFFAOYSA-I
Pentetate zinc trisodiumNXU65IC8PG11082-38-5HVASDHJNLYRZEA-UHFFFAOYSA-I
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Draximage DtpaInjection, powder, lyophilized, for solution20 mg/1Intravenous; Respiratory (inhalation)Jubilant Draximage Inc.1989-12-29Not applicableUs
Kit for the Preparation of Technetium Tc 99m Pentetate InjectionInjection20.6 mg/10mLIntravenousPharmalucence, Inc.1976-11-162010-08-02Us
Pentetate calcium trisodiumInjection, solution, concentrate1000 mg/5mLIntravenous; Respiratory (inhalation)Hameln Pharma Plus Gmbh2004-08-11Not applicableUs
Pentetate Calcium TrisodiumInjection, solution, concentrate200 mg/1mLIntravenous; Respiratory (inhalation)Hameln Pharmaceuticals2006-12-18Not applicableUs
Pentetate Zinc TrisodiumInjection, solution, concentrate200 mg/1mLIntravenous; Respiratory (inhalation)Hameln Pharmaceuticals2006-12-18Not applicableUs
Pentetate zinc trisodiumInjection, solution, concentrate1000 mg/5mLIntravenous; Respiratory (inhalation)Hameln Pharma Plus Gmbh2004-08-11Not applicableUs
Pentetic AcidInjection20 mg/1IntravenousJubilant HollisterStier General Partnership1989-12-29Not applicableUs
Categories
UNII
7A314HQM0I
CAS number
67-43-6
Weight
Average: 393.349
Monoisotopic: 393.138343953
Chemical Formula
C14H23N3O10
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

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
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
Human
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.[7]It 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]

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
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.
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.
AdefovirAdefovir may decrease the excretion rate of Pentetic acid which could result in a higher serum level.
Food Interactions
Not Available

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]
External Links
ChemSpider
2945
ChEBI
35739
ChEMBL
CHEMBL780
Wikipedia
Pentetate
FDA label
Download (204 KB)
MSDS
Download (232 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2TerminatedTreatmentArthralgia/joint pain / Cognitive Impairments / Headaches / Skin hyperpigmentation1
3CompletedPreventionPneumococcal Diseases / Streptococcal Infections / Streptococcus Pneumoniae1
3CompletedPreventionStreptococcal Infections1
Not AvailableActive Not RecruitingNot AvailableLung Cancers1
Not AvailableCompletedNot AvailableAcellular Pertussis / Diphteria, Tetanus and Pertussis / Diphtheria / Tetanus1

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, solution, concentrateIntravenous; Respiratory (inhalation)1000 mg/5mL
Injection, solution, concentrateIntravenous; Respiratory (inhalation)200 mg/1mL
InjectionIntravenous20 mg/1
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

Taxonomy

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
Pentacarboxylic acid or derivatives / Alpha-amino acid / Alpha-amino acid or derivatives / Amino acid or derivatives / Tertiary amine / Tertiary aliphatic amine / Amino acid / Carboxylic acid / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
pentacarboxylic acid (CHEBI:35739)

Targets

1. Transuranium elements
Kind
Group
Organism
Human
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
Human
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 November 02, 2018 09:14