Identification

Name
Potassium perchlorate
Accession Number
DB09418
Type
Small Molecule
Groups
Approved, Investigational
Description

Potassium perchlorate is an inorganic salt with the chemical formula KClO4. It is a strong oxidizer with the lowest solubility of the alkali metal perchlorates. Potassium is most commonly used in flares and automobile airbags [1]. The use of potassium perchlorate as a component in sealing gaskets for food containers has been revoked by the FDA following the use being abandoned by the industry [7]. Potassium perchlorate acts as a competitive inhibitor of iodine uptake by the thyroid gland and attenuates the production of the thyroid hormone. Thus the use of potassium perchlorate has been extensive for hyperthyroidism during the last 50 years, particularly in the late 1950s and early 1960s [1]. The therapeutic use of potassium perchlorate in thyroid disorders has been ceased due to a high risk for developing aplastic anemia and nephrotic syndrome [6].

Structure
Thumb
Synonyms
  • Perchloric acid, potassium salt
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Perchloracap Capsule 200mgCapsule200 mgOralTyco Healthcare1989-12-312010-01-07Canada
Categories
UNII
42255P5X4D
CAS number
7778-74-7
Weight
Average: 138.549
Monoisotopic: 137.912218056
Chemical Formula
ClKO4
InChI Key
YLMGFJXSLBMXHK-UHFFFAOYSA-M
InChI
InChI=1S/ClHO4.K/c2-1(3,4)5;/h(H,2,3,4,5);/q;+1/p-1
IUPAC Name
potassium perchlorate
SMILES
[K+].[O-][Cl](=O)(=O)=O

Pharmacology

Indication

No current FDA- or EMA-approved therapeutic indications.

Pharmacodynamics

Potassium perchlorate inhibits thyroid iodide transport. The clinical use of potassium perchlorate in hyperthyroidism, such as Graves' disease and amiodarone-induced hypothyroidism, have been investigated in various studies. Thyroid dysfunction occurs in about 15-20% of the patients receiving long-term amiodarone therapy [2]. In patients with amiodarone-induced hypothyroidism, short-term administration of potassium perchlorate resulted in restoration of euthyroidism in most patients [4]. Euthyroidism promoted by potassium perchlorate does not persist unless amiodarone treatment is withdrawn [2].

Mechanism of action

Thyroxine (T4) and tri-iodothyronine (T3) are major thyroid hormones, or iodothyronines, that are synthesized and released from the thyroid. Iodine plays an essential role in the synthesis of these hormones. Via the sodium-iodide symporter (NIS), which is a protein located on the basolateral membrane of the thyroid follicular cell, iodine is transported from the blood into the thyroid gland where it is oxidized to [3]. Perchlorate (ClO4−) is the dissociated anion of potassium perchlorate that exerts an inhibitory effect on iodide uptake by the thyroid gland in the cellular level [3]. Due to its similarity in ionic size and charge to iodide, perchlorate inhibits the sodium-iodide symporter (NIS) without being translocated into the thyroid follicular cell [3]. The inhibition constant, Ki, is estimated as 0.4 µmol to 24 µmol. At therapeutic dosage levels this competitive inhibition decreases the entrance of iodide into the thyroid, resulting in less available iodide for hormone synthesis and, therefore, a decrease in T3 and T4 synthesis [3]. When ambient iodine intake is low or iodide uptake is sufficiently inhibited, perchlorate is capable in inducing goiter and hypothyroidism from inhibited iodide uptake [3]. At high doses of potassium perchlorate, reduced T3 and T4 levels may be accompanied by increased TSH levels via a negative feedback loop, affecting the thyroid, pituitary and hypothalamus [8].

TargetActionsOrganism
ASodium/iodide cotransporter
inhibitor
Human
Absorption

Perchlorate is rapidly absorbed from the gastrointestinal (GI) tract after ingestion [3]. The time to reach peak plasma levels of perchlorate is approximately 3 hours following oral administration [6]. As potassium perchlorate is an organic compound with complete ionization in water, dermal absorption through intact skin is unlikely [8].

Volume of distribution

No pharmacokinetic data on the volume of distribution. Perchlorate is likely to sequester into the thyroid gland, gastrointestinal tract, and possibly the skin [5].

Protein binding

Displacement studies with thyroid hormones suggest that perchlorate ions may interfere with the binding of T4 to serum proteins [5].

Metabolism

Perchlorate ions are not reported to undergo metabolism [6].

Route of elimination

Perchlorate is mainly excreted unchanged in the urine with the recovery rate of approximately 95% within 72 hours [3]. It is reported that half of the total perchlorate ions administered orally are excreted during the first 5 hours post-dosing while the rest of the dose is excreted within 48 to 72 hours [6].

Half life

Perchlorate has a half-life in humans of approximately 6 to 8 hours [3].

Clearance

No pharmacokinetic data on clearance rate. Systemic clearance is biphasic with a slow terminal phase [5].

Toxicity

In a mice study, the LD50 was reported as 3621 mg/kg of following 33 weeks of oral administration [9]. A study reports that at doses of 400 mg/d for several weeks had adverse effects such as GI irritation, skin rash, and lymphadenopathy but cited no serious complications [3]. In patients treated with 400 to 1,000 mg perchlorate daily, cases of agranulocytosis and fatal aplastic anemia have been reported. Several deaths from aplastic anemia in patients treated with perchlorate at doses of 400 to 1000 mg/d for 8 to 33 weeks were also reported [3]. The last report of fatal bone marrow toxicity related to treatment with potassium perchlorate was in the 1960s [3].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolPotassium perchlorate may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
AlmotriptanAlmotriptan may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
AlprazolamAlprazolam may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
AmantadineAmantadine may decrease the excretion rate of Potassium perchlorate which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Potassium perchlorate which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylinePotassium perchlorate may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Connell JM: Long-term use of potassium perchlorate. Postgrad Med J. 1981 Aug;57(670):516-7. [PubMed:6272249]
  2. Bogazzi F, Bartalena L, Tomisti L, Dell'Unto E, Cosci C, Sardella C, Tanda ML, Lai A, Gasperi M, Aghini-Lombardi F, Martino E: Potassium perchlorate only temporarily restores euthyroidism in patients with amiodarone-induced hypothyroidism who continue amiodarone therapy. J Endocrinol Invest. 2008 Jun;31(6):515-9. doi: 10.1007/BF03346400. [PubMed:18591883]
  3. Soldin OP, Braverman LE, Lamm SH: Perchlorate clinical pharmacology and human health: a review. Ther Drug Monit. 2001 Aug;23(4):316-31. [PubMed:11477312]
  4. Martino E, Mariotti S, Aghini-Lombardi F, Lenziardi M, Morabito S, Baschieri L, Pinchera A, Braverman L, Safran M: Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism. J Clin Endocrinol Metab. 1986 Nov;63(5):1233-6. doi: 10.1210/jcem-63-5-1233. [PubMed:3020079]
  5. Yu KO, Narayanan L, Mattie DR, Godfrey RJ, Todd PN, Sterner TR, Mahle DA, Lumpkin MH, Fisher JW: The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat. Toxicol Appl Pharmacol. 2002 Jul 15;182(2):148-59. [PubMed:12140178]
  6. POTASSIUM PERCHLORATE - National Library of Medicine HSDB Database - Toxnet [Link]
  7. FDA is Revoking Food Additive Approval for the Use of Perchlorate in Sealing Gaskets for Food Containers Because its Use Has Been Abandoned [Link]
  8. Perchlorate Toxicity and Risk Assessment [Link]
  9. Toxicological Profile For Perchlorates [Link]
External Links
PubChem Compound
516900
PubChem Substance
347827848
ChemSpider
22913
ChEMBL
CHEMBL1200696
Wikipedia
Potassium_perchlorate
ATC Codes
H03BC01 — Potassium perchlorate
MSDS
Download (49.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingPreventionHeart Failure, Unspecified1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral200 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Decomposes at 400 °CMSDS
water solubility17 g/L at 20 °CMSDS
Predicted Properties
PropertyValueSource
Water Solubility102.0 mg/mLALOGPS
logP-0.97ALOGPS
logP-0.098ChemAxon
logS-0.13ALOGPS
pKa (Strongest Acidic)-7.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area74.27 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity11.91 m3·mol-1ChemAxon
Polarizability5.23 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of inorganic compounds known as alkali metal perchlorates. These are inorganic compounds in which the largest oxoanion is perchlorate, and in which the heaviest atom not in an oxoanion is an alkali metal.
Kingdom
Inorganic compounds
Super Class
Mixed metal/non-metal compounds
Class
Alkali metal oxoanionic compounds
Sub Class
Alkali metal perchlorates
Direct Parent
Alkali metal perchlorates
Alternative Parents
Inorganic salts / Inorganic oxides
Substituents
Alkali metal perchlorate / Inorganic oxide / Inorganic salt
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Mediates iodide uptake in the thyroid gland.
Specific Function
Iodide transmembrane transporter activity
Gene Name
SLC5A5
Uniprot ID
Q92911
Uniprot Name
Sodium/iodide cotransporter
Molecular Weight
68665.63 Da
References
  1. Soldin OP, Braverman LE, Lamm SH: Perchlorate clinical pharmacology and human health: a review. Ther Drug Monit. 2001 Aug;23(4):316-31. [PubMed:11477312]
  2. Perchlorate Toxicity and Risk Assessment [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Yamada T, Jones AE: Effect of thiocyanate, perchlorate and other anions on plasma protein-thyroid hormone interaction in vitro. Endocrinology. 1968 Jan;82(1):47-53. doi: 10.1210/endo-82-1-47. [PubMed:4169405]
  2. SCATCHARD G, BLACK ES: The effect of salts on the isoionic and isoelectric points of proteins. J Phys Colloid Chem. 1949 Jan;53(1):88-99. [PubMed:18124175]
  3. Yu KO, Narayanan L, Mattie DR, Godfrey RJ, Todd PN, Sterner TR, Mahle DA, Lumpkin MH, Fisher JW: The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat. Toxicol Appl Pharmacol. 2002 Jul 15;182(2):148-59. [PubMed:12140178]

Drug created on November 30, 2015 12:10 / Updated on October 01, 2018 14:50