Identification

Name
Ciclopirox
Accession Number
DB01188  (APRD00871)
Type
Small Molecule
Groups
Approved, Investigational
Description

Ciclopirox olamine (used in preparations called Batrafen, Loprox, Mycoster, Penlac and Stieprox) is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against Tinea versicolor. [Wikipedia]

Structure
Thumb
Synonyms
  • 6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone
  • ciclopirox
  • Ciclopiroxum
External IDs
HOE 296B / HOE-296B
Product Ingredients
IngredientUNIICASInChI Key
Ciclopirox olamine50MD4SB4AP41621-49-2MBRHNTMUYWQHMR-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CiclopiroxGel7.7 mg/1gTopicalAlvogen, Inc.2017-02-14Not applicableUs
CiclopiroxGel7.7 mg/1gTopicalPaddock Laboratories, Inc.2009-01-152013-03-24Us
Ciclopirox OlamineCream7.7 mg/1gTopicalGlades Pharmaceuticals, LLC2009-12-312010-01-01Us
Ciclopirox Topical SolutionSolution8 %TopicalSterimax Inc2013-09-16Not applicableCanada
LoproxCream7.7 mg/1gTopicalMedicis Pharmaceutical Corporation2005-04-012008-10-01Us
LoproxKit7.7 mg/1mLMedimetriks Pharmaceuticals2016-10-14Not applicableUs
LoproxCream7.7 mg/1gTopicalMedimetriks Pharmaceuticals2016-01-14Not applicableUs
LoproxSuspension7.7 mg/1mLTopicalMedicis Pharmaceutical Corporation2002-09-112008-10-01Us
LoproxCream7.7 mg/1gTopicalPhysicians Total Care, Inc.1982-12-302006-12-31Us
LoproxSuspension7.7 mg/1mLTopicalMedimetriks Pharmaceuticals2016-10-14Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ciclopiroxSolution8 %TopicalApotex Corporation2008-04-18Not applicableCanada
CiclodanSolution2.28 g/1mLTopicalMedimetriks Pharmaceuticals2011-04-10Not applicableUs
CiclodanCream7.7 mg/1gTopicalMedimetriks Pharmaceuticals2012-06-152017-12-01Us
CiclodanSolution2.28 g/1mLTopicalMedimetriks Pharmaceuticals2011-04-10Not applicableUs
CiclodanKit7.7 mg/1gMedimetriks Pharmaceuticals2012-06-152017-12-01Us
CiclopiroxSolution80 mg/1mLTopicalHarris Pharmaceutical, Inc.2007-09-192017-11-30Us
CiclopiroxSolution71.3 mg/1mLTopicalRebel Distributors2007-09-18Not applicableUs
CiclopiroxShampoo10 mg/0.96mLTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2010-05-25Not applicableUs
CiclopiroxShampoo10 mg/0.96mLTopicalTeligent Pharma, Inc.2018-04-05Not applicableUs
CiclopiroxSuspension7.7 mg/1mLTopicalTaro Pharmaceuticals U.S.A., Inc.2005-08-10Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PedipakCiclopirox (71.3 mg/1mL) + Urea (17 g/85g)KitTotal Pharmacy Supply, Inc.2007-09-182015-10-05Us
Pedipirox-4 Nail KitCiclopirox (71.3 mg/1mL) + Ciclopirox (71.3 mg/1mL)KitPedinol Pharmacal, Inc.2012-02-032015-04-30Us
Pedipirox-4 Nail KitCiclopirox (71.3 mg/1mL) + Ciclopirox (71.3 mg/1mL)KitPedinol Pharmacal, Inc.2012-02-032015-04-30Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CiclopiroxCiclopirox (2.28 g/1mL)KitAcella Pharmaceuticals, LLC2011-10-10Not applicableUs
CiclopiroxCiclopirox (8 g/100mL)SolutionTopicalDr Marc's Manufacturing And Sales2018-01-302018-04-18Us
CiclopiroxCiclopirox (80 mg/1mL) + Tocopherol (50 mg/1)KitAcella Pharmaceuticals, LLC2008-10-272015-05-31Us
Terbinafine HCl CiclopiroxCiclopirox (4 g/100mL) + Terbinafine Hydrochloride (4 g/100mL)SolutionTopicalDr Marc's Manufacturing And Sales2018-01-302018-04-18Us
International/Other Brands
Batrafen (Sanofi) / Mycoster (Pierre Fabre) / Stieprox (Stiefel)
Categories
UNII
19W019ZDRJ
CAS number
29342-05-0
Weight
Average: 207.2689
Monoisotopic: 207.125928793
Chemical Formula
C12H17NO2
InChI Key
SCKYRAXSEDYPSA-UHFFFAOYSA-N
InChI
InChI=1S/C12H17NO2/c1-9-7-11(13(15)12(14)8-9)10-5-3-2-4-6-10/h7-8,10,15H,2-6H2,1H3
IUPAC Name
6-cyclohexyl-1-hydroxy-4-methyl-1,2-dihydropyridin-2-one
SMILES
CC1=CC(=O)N(O)C(=C1)C1CCCCC1

Pharmacology

Indication

Used as a topical treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to Trichophyton rubrum.

Associated Conditions
Pharmacodynamics

Ciclopirox is a broad-spectrum antifungal medication that also has antibacterial and anti-inflammatory properties. Its main mode of action is thought to be its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. Ciclopirox exhibits either fungistatic or fungicidal activity in vitro against a broad spectrum of fungal organisms, such as dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. In addition to its broad spectrum of action, ciclopirox also exerts antibacterial activity against many Gram-positive and Gram-negative bacteria. Furthermore, the anti-inflammatory effects of ciclopirox have been demonstrated in human polymorphonuclear cells, where ciclopirox has inhibited the synthesis of prostaglandin and leukotriene. Ciclopirox can also exhibit its anti-inflammatory effects by inhibiting the formation of 5-lipoxygenase and cyclooxygenase.

Mechanism of action

Unlike antifungals such as itraconazole and terbinafine, which affect sterol synthesis, ciclopirox is thought to act through the chelation of polyvalent metal cations, such as Fe3+ and Al3+. These cations inhibit many enzymes, including cytochromes, thus disrupting cellular activities such as mitochondrial electron transport processes and energy production. Ciclopirox also appears to modify the plasma membrane of fungi, resulting in the disorganization of internal structures. The anti-inflammatory action of ciclopirox is most likely due to inhibition of 5-lipoxygenase and cyclooxygenase. ciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1
binder
Human
Absorption

Rapidly absorbed after oral administration. Mean absorption of ciclopirox after application to nails of all twenty digits and adjacent 5 millimeters of skin once daily for 6 months in patients with dermatophytic onychomycoses was less than 5% of the applied dose. Ciclopirox olamine also penetrates into hair and through the epidermis and hair follicles into sebaceous glands and dermis.

Volume of distribution
Not Available
Protein binding

Protein binding is 94-97% following topical administration.

Metabolism

Glucuronidation is the main metabolic pathway of ciclopirox.

Route of elimination

Most of the compound is excreted either unchanged or as glucuronide. After oral administration of 10 mg of radiolabeled drug (14C-ciclopirox) to healthy volunteers, approximately 96% of the radioactivity was excreted renally within 12 hours of administration. Ninety-four percent of the renally excreted radioactivity was in the form of glucuronides.

Half life

1.7 hours for 1% topical solution.

Clearance
Not Available
Toxicity

Oral LD50 in rat is >10 ml/kg. Symptoms of overexposure include drowsiness and headache.

Affected organisms
  • Humans and other mammals
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

Lohaus, G.and Dittmar, W.; U.S. Patents 3,972,888; August 3, 1976; and 3,883,545; May 13, 1975; both assigned to Hoechst A .G.

General References
  1. Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC, Hube B: Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob Agents Chemother. 2003 Jun;47(6):1805-17. [PubMed:12760852]
  2. Sigle HC, Thewes S, Niewerth M, Korting HC, Schafer-Korting M, Hube B: Oxygen accessibility and iron levels are critical factors for the antifungal action of ciclopirox against Candida albicans. J Antimicrob Chemother. 2005 May;55(5):663-73. Epub 2005 Mar 24. [PubMed:15790671]
External Links
Human Metabolome Database
HMDB0015319
KEGG Drug
D01364
PubChem Compound
2749
PubChem Substance
46506333
ChemSpider
2647
BindingDB
66087
ChEBI
453011
ChEMBL
CHEMBL1413
Therapeutic Targets Database
DAP000466
PharmGKB
PA164747060
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ciclopirox
ATC Codes
G01AX12 — CiclopiroxD01AE14 — Ciclopirox
AHFS Codes
  • 84:04.08.20 — Hydroxypyridones
FDA label
Download (422 KB)
MSDS
Download (74.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / Hodgkins Disease (HD) / Leukemia Acute Myeloid Leukemia (AML) / Malignancies, Hematologic / Myelodysplasia1
2RecruitingTreatmentOnychomycosis1
3CompletedTreatmentTinea Pedis1
3Not Yet RecruitingSupportive CareOnychomycosis1
3RecruitingNot AvailableDistal Subungual Onychomycosis1
3RecruitingTreatmentSevere Seborrheic Dermatitis1
4CompletedTreatmentOnychomycosis1
4TerminatedNot AvailableDermatomycoses1
4Unknown StatusTreatmentOnychomycosis1
4Unknown StatusTreatmentQuality of Life / Seborrheic Dermatitis1
Not AvailableCompletedTreatmentTinea Pedis1
Not AvailableWithdrawnPreventionVulvar Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Brookstone Pharmaceuticals
  • Cipla Ltd.
  • Contract Pharm
  • Dermik Labs
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • E. Fougera and Co.
  • G & W Labs
  • Glenmark Generics Ltd.
  • Groupe Parima Inc.
  • Harris Pharmaceutical Inc.
  • Hi Tech Pharmacal Co. Inc.
  • JSJ Pharmaceuticals Inc.
  • Medicis Pharmaceutical Co.
  • Medisca Inc.
  • Nycomed Inc.
  • Paddock Labs
  • Patheon Inc.
  • Perrigo Co.
  • Pharmedix
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Sandoz
  • Sanofi-Aventis Inc.
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Tolmar Inc.
Dosage forms
FormRouteStrength
GelTopical7.7 mg/1g
GelTopical7.70 mg/1g
Kit
Kit2.28 g/1mL
LotionTopical7.7 mg/1mL
ShampooOral10 mg/0.96mL
ShampooTopical1 g/100mL
ShampooTopical10 mg/.96mL
ShampooTopical10 mg/0.96mL
SolutionTopical71.3 mg/1mL
SolutionTopical8 g/100mL
SolutionTopical80 mg/1mL
SolutionTopical80 mg/1g
CreamTopical7.7 mg/1g
SuspensionTopical7.70 mg/100mL
SolutionTopical2.28 g/1mL
Kit7.7 mg/1mL
Kit7.7 mg/1g
SuspensionTopical7.7 mg/1mL
CreamTopical1 %
CreamTopical10 mg
LotionTopical1 %
LotionTopical10 mg
Kit71.3 mg/1mL
SolutionTopical8 %
ShampooTopical1.5 %
SolutionTopical
Prices
Unit descriptionCostUnit
Loprox 0.77% Gel 100 gm Jar447.91USD jar
Loprox 0.77% Cream 90 gm Tube266.01USD tube
Ciclopirox 0.77% Gel 100 gm Tube252.1USD tube
Penlac 8% Solution 6.6ml Bottle244.87USD bottle
Loprox 1% Shampoo 120ml Bottle235.49USD bottle
Loprox 0.77% Suspension 60ml Bottle223.11USD bottle
Loprox 0.77% Gel 45 gm Tube219.21USD tube
Ciclopirox 8% Solution 6.6ml Bottle177.27USD bottle
Loprox 0.77% Gel 30 gm Tube155.63USD tube
Ciclopirox 1% Shampoo 120ml Bottle153.24USD bottle
Ciclopirox Olamine 0.77% Cream 90 gm Tube128.77USD tube
Ciclopirox 0.77% Gel 45 gm Tube125.88USD tube
Loprox 0.77% Cream 30 gm Tube107.88USD tube
Ciclopirox Olamine 0.77% Suspension 60ml Bottle100.0USD bottle
Ciclopirox 0.77% Gel 30 gm Tube83.91USD tube
Ciclopirox Olamine 0.77% Cream 30 gm Tube53.24USD tube
Ciclopirox Olamine 0.77% Suspension 30ml Bottle50.48USD bottle
Penlac 8% solution39.24USD ml
Ciclopirox Olamine 0.77% Cream 15 gm Tube29.8USD tube
Ciclopirox olamine powder10.47USD g
Loprox 0.77% cream2.96USD g
Ciclopirox 0.77% cream1.64USD g
Loprox 1 % Cream0.53USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7026337No2006-04-112016-11-21Us
US7018656No2006-03-282018-09-05Us
US7981909No2011-07-192017-09-16Us
US8227490No2012-07-242017-09-16Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)143Lohaus, G.and Dittmar, W.; U.S. Patents 3,972,888; August 3, 1976; and 3,883,545; May 13, 1975; both assigned to Hoechst A .G.
logP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.41 mg/mLALOGPS
logP2.15ALOGPS
logP2.22ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)6.84ChemAxon
pKa (Strongest Basic)-6.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity60.91 m3·mol-1ChemAxon
Polarizability23.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.9892
Caco-2 permeable+0.5125
P-glycoprotein substrateNon-substrate0.731
P-glycoprotein inhibitor INon-inhibitor0.7715
P-glycoprotein inhibitor IINon-inhibitor0.9497
Renal organic cation transporterNon-inhibitor0.8234
CYP450 2C9 substrateNon-substrate0.6075
CYP450 2D6 substrateNon-substrate0.8043
CYP450 3A4 substrateSubstrate0.6051
CYP450 1A2 substrateInhibitor0.5732
CYP450 2C9 inhibitorNon-inhibitor0.5951
CYP450 2D6 inhibitorNon-inhibitor0.8998
CYP450 2C19 inhibitorNon-inhibitor0.6613
CYP450 3A4 inhibitorNon-inhibitor0.873
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5218
Ames testNon AMES toxic0.6085
CarcinogenicityNon-carcinogens0.9004
BiodegradationNot ready biodegradable0.802
Rat acute toxicity2.3495 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9727
hERG inhibition (predictor II)Non-inhibitor0.5929
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyridinones. These are compounds containing a pyridine ring, which bears a ketone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Pyridinones
Alternative Parents
Methylpyridines / Dihydropyridines / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Methylpyridine / Pyridinone / Dihydropyridine / Heteroaromatic compound / Lactam / Azacycle / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
hydroxypyridone antifungal drug, pyridone, cyclic hydroxamic acid (CHEBI:453011)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Steroid hormone binding
Specific Function
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  1. Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC, Hube B: Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob Agents Chemother. 2003 Jun;47(6):1805-17. [PubMed:12760852]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:52