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Identification
NameRoflumilast
Accession NumberDB01656  (EXPT02802)
TypeSmall Molecule
GroupsApproved
DescriptionRoflumilast is a phosphodiesterase-4 (PDE-4) inhibitor. Due to its selective inhibition of the PDE4 isoenzyme in lung cells, roflumilast is indicated for the management of chronic obstrtuctive pulmonary disease (COPD) exacerbations. Treatment with Roflumilast is associated with an increase in psychiatric adverse reactions, including suicide and suicidal attempts.
Structure
Thumb
Synonyms
Daliresp
ROF
Roflumilastum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DalirespTablet500 ug/1OralAstra Zeneca Pharmaceuticals Lp2015-07-01Not applicableUs
DalirespTablet500 ug/1OralCardinal Health2011-02-28Not applicableUs
DalirespTablet500 ug/1OralForest Laboratories, Inc.2011-02-28Not applicableUs
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet500 mcgOralTakeda Canada Inc2010-12-30Not applicableCanada
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
DaxasTablet, film coated500 μgOralTakeda Gmb H2010-07-05Not applicableEu
LibertekTablet, film coated500 μgOralTakeda Gmb H2011-02-28Not applicableEu
LibertekTablet, film coated500 μgOralTakeda Gmb H2011-02-28Not applicableEu
LibertekTablet, film coated500 μgOralTakeda Gmb H2011-02-28Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0P6C6ZOP5U
CAS number162401-32-3
WeightAverage: 403.207
Monoisotopic: 402.034954148
Chemical FormulaC17H14Cl2F2N2O3
InChI KeyMNDBXUUTURYVHR-UHFFFAOYSA-N
InChI
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)
IUPAC Name
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
SMILES
FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl
Pharmacology
IndicationRoflumilast is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm.
Structured Indications
PharmacodynamicsRoflumilast (and its active metabolite, roflumilast N-oxide) increases cyclic adenosine-3′, 5′-monophosphate (cAMP) in lung cells by inhibiting PDE4. Increased cAMP activates PKA, which inactivates transcription factors involved in inflammation. Romflumilast also decreases the amount of sputum neutrophils and eosinophils in COPD patients.
Mechanism of actionRoflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast.
TargetKindPharmacological actionActionsOrganismUniProt ID
cAMP-specific 3',5'-cyclic phosphodiesterase 4DProteinunknown
inhibitor
HumanQ08499 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4AProteinunknown
inhibitor
HumanP27815 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4BProteinunknown
inhibitor
HumanQ07343 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4CProteinunknown
inhibitor
HumanQ08493 details
Related Articles
AbsorptionAfter a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours. While in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged.
Volume of distribution

Roflumilast has a Vd of 2.9L/kg with a dose of 500mcg. Permeability of roflumilast across the blood-brain barrier appears to be poor in rat studies.

Protein bindingRoflumilast is 99% plasma protein bound.
Metabolism

Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2.

SubstrateEnzymesProduct
Roflumilast
Not Available
Roflumilast N-oxideDetails
Route of eliminationRoflumilast is excreted 70% in the urine as roflumilast N-oxide.
Half lifePlasma half-life of roflumilast is 17 hours and its metabolite is 30 hours (oral dose).
Clearance

~9.6 L/hour.

ToxicityHeadache, weight loss, GI upset, insomnia, and loose stools.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
2-MethoxyethanolRoflumilast may increase the immunosuppressive activities of 2-Methoxyethanol.Experimental
9-(2-phosphonylmethoxyethyl)-2,6-diaminopurineRoflumilast may increase the immunosuppressive activities of 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine.Investigational
AbataceptRoflumilast may increase the immunosuppressive activities of Abatacept.Approved
abetimusRoflumilast may increase the immunosuppressive activities of abetimus.Investigational
ABR-215757Roflumilast may increase the immunosuppressive activities of ABR-215757.Investigational
ActeosideRoflumilast may increase the immunosuppressive activities of Acteoside.Investigational
AdalimumabRoflumilast may increase the immunosuppressive activities of Adalimumab.Approved
Adefovir DipivoxilRoflumilast may increase the immunosuppressive activities of Adefovir Dipivoxil.Approved, Investigational
AfelimomabRoflumilast may increase the immunosuppressive activities of Afelimomab.Investigational
AlefaceptRoflumilast may increase the immunosuppressive activities of Alefacept.Approved, Withdrawn
AlemtuzumabRoflumilast may increase the immunosuppressive activities of Alemtuzumab.Approved, Investigational
alicaforsenRoflumilast may increase the immunosuppressive activities of alicaforsen.Investigational
AltretamineRoflumilast may increase the immunosuppressive activities of Altretamine.Approved
Amg 827Roflumilast may increase the immunosuppressive activities of Amg 827.Investigational
AmsacrineRoflumilast may increase the immunosuppressive activities of Amsacrine.Approved
AnakinraRoflumilast may increase the immunosuppressive activities of Anakinra.Approved
Anti-thymocyte Globulin (Rabbit)Roflumilast may increase the immunosuppressive activities of Anti-thymocyte Globulin (Rabbit).Approved
ApremilastRoflumilast may increase the immunosuppressive activities of Apremilast.Approved, Investigational
AzacitidineRoflumilast may increase the immunosuppressive activities of Azacitidine.Approved, Investigational
AzathioprineRoflumilast may increase the immunosuppressive activities of Azathioprine.Approved
BasiliximabRoflumilast may increase the immunosuppressive activities of Basiliximab.Approved, Investigational
BelataceptRoflumilast may increase the immunosuppressive activities of Belatacept.Approved
BelimumabRoflumilast may increase the immunosuppressive activities of Belimumab.Approved
BenznidazoleRoflumilast may increase the immunosuppressive activities of Benznidazole.Investigational
BetamethasoneRoflumilast may increase the immunosuppressive activities of Betamethasone.Approved, Vet Approved
BleomycinRoflumilast may increase the immunosuppressive activities of Bleomycin.Approved
BlinatumomabRoflumilast may increase the immunosuppressive activities of Blinatumomab.Approved
Brentuximab vedotinRoflumilast may increase the immunosuppressive activities of Brentuximab vedotin.Approved
BriakinumabRoflumilast may increase the immunosuppressive activities of Briakinumab.Investigational
BudesonideRoflumilast may increase the immunosuppressive activities of Budesonide.Approved
BusulfanRoflumilast may increase the immunosuppressive activities of Busulfan.Approved, Investigational
C1 Esterase Inhibitor (Human)Roflumilast may increase the immunosuppressive activities of C1 Esterase Inhibitor (Human).Approved
CabazitaxelRoflumilast may increase the immunosuppressive activities of Cabazitaxel.Approved
CanakinumabRoflumilast may increase the immunosuppressive activities of Canakinumab.Approved, Investigational
CapecitabineRoflumilast may increase the immunosuppressive activities of Capecitabine.Approved, Investigational
CarbamazepineThe serum concentration of Roflumilast can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarboplatinRoflumilast may increase the immunosuppressive activities of Carboplatin.Approved
CarmustineRoflumilast may increase the immunosuppressive activities of Carmustine.Approved
CastanospermineRoflumilast may increase the immunosuppressive activities of Castanospermine.Experimental
Certolizumab pegolRoflumilast may increase the immunosuppressive activities of Certolizumab pegol.Approved
ChlorambucilRoflumilast may increase the immunosuppressive activities of Chlorambucil.Approved
CimetidineThe serum concentration of the active metabolites of Roflumilast can be increased when Roflumilast is used in combination with Cimetidine.Approved
CiprofloxacinThe serum concentration of Roflumilast can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CisplatinRoflumilast may increase the immunosuppressive activities of Cisplatin.Approved
CladribineRoflumilast may increase the immunosuppressive activities of Cladribine.Approved, Investigational
ClofarabineRoflumilast may increase the immunosuppressive activities of Clofarabine.Approved, Investigational
CorticotropinRoflumilast may increase the immunosuppressive activities of Corticotropin.Approved, Vet Approved
Cortisone acetateRoflumilast may increase the immunosuppressive activities of Cortisone acetate.Approved
CyclophosphamideRoflumilast may increase the immunosuppressive activities of Cyclophosphamide.Approved, Investigational
CyclosporineRoflumilast may increase the immunosuppressive activities of Cyclosporine.Approved, Investigational, Vet Approved
CytarabineRoflumilast may increase the immunosuppressive activities of Cytarabine.Approved, Investigational
DacarbazineRoflumilast may increase the immunosuppressive activities of Dacarbazine.Approved, Investigational
DaclizumabRoflumilast may increase the immunosuppressive activities of Daclizumab.Approved, Investigational
DactinomycinRoflumilast may increase the immunosuppressive activities of Dactinomycin.Approved
DasatinibRoflumilast may increase the immunosuppressive activities of Dasatinib.Approved, Investigational
DaunorubicinRoflumilast may increase the immunosuppressive activities of Daunorubicin.Approved
DeoxyspergualinRoflumilast may increase the immunosuppressive activities of Deoxyspergualin.Investigational
DexamethasoneRoflumilast may increase the immunosuppressive activities of Dexamethasone.Approved, Investigational, Vet Approved
Dimethyl fumarateRoflumilast may increase the immunosuppressive activities of Dimethyl fumarate.Approved, Investigational
DinutuximabRoflumilast may increase the immunosuppressive activities of Dinutuximab.Approved
DocetaxelRoflumilast may increase the immunosuppressive activities of Docetaxel.Approved, Investigational
DoxifluridineRoflumilast may increase the immunosuppressive activities of Doxifluridine.Investigational
DoxorubicinRoflumilast may increase the immunosuppressive activities of Doxorubicin.Approved, Investigational
EculizumabRoflumilast may increase the immunosuppressive activities of Eculizumab.Approved, Investigational
EfalizumabRoflumilast may increase the immunosuppressive activities of Efalizumab.Approved, Investigational
EnzalutamideThe serum concentration of Roflumilast can be decreased when it is combined with Enzalutamide.Approved
EpirubicinRoflumilast may increase the immunosuppressive activities of Epirubicin.Approved
EstramustineRoflumilast may increase the immunosuppressive activities of Estramustine.Approved
EtanerceptRoflumilast may increase the immunosuppressive activities of Etanercept.Approved, Investigational
EtoposideRoflumilast may increase the immunosuppressive activities of Etoposide.Approved
EverolimusRoflumilast may increase the immunosuppressive activities of Everolimus.Approved
FingolimodRoflumilast may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FloxuridineRoflumilast may increase the immunosuppressive activities of Floxuridine.Approved
FludarabineRoflumilast may increase the immunosuppressive activities of Fludarabine.Approved
FludrocortisoneRoflumilast may increase the immunosuppressive activities of Fludrocortisone.Approved
FluorouracilRoflumilast may increase the immunosuppressive activities of Fluorouracil.Approved
FluvoxamineThe serum concentration of the active metabolites of Roflumilast can be increased when Roflumilast is used in combination with Fluvoxamine.Approved, Investigational
FosphenytoinThe serum concentration of Roflumilast can be decreased when it is combined with Fosphenytoin.Approved
Gallium nitrateRoflumilast may increase the immunosuppressive activities of Gallium nitrate.Approved, Investigational
GemcitabineRoflumilast may increase the immunosuppressive activities of Gemcitabine.Approved
Gemtuzumab ozogamicinRoflumilast may increase the immunosuppressive activities of Gemtuzumab ozogamicin.Approved, Investigational, Withdrawn
Glatiramer AcetateRoflumilast may increase the immunosuppressive activities of Glatiramer Acetate.Approved, Investigational
GlimepirideRoflumilast may increase the immunosuppressive activities of Glimepiride.Approved
GolimumabRoflumilast may increase the immunosuppressive activities of Golimumab.Approved
GusperimusRoflumilast may increase the immunosuppressive activities of Gusperimus.Investigational
HydrocortisoneRoflumilast may increase the immunosuppressive activities of Hydrocortisone.Approved, Vet Approved
HydroxyureaRoflumilast may increase the immunosuppressive activities of Hydroxyurea.Approved
Ibritumomab tiuxetanRoflumilast may increase the immunosuppressive activities of Ibritumomab tiuxetan.Approved
IbrutinibRoflumilast may increase the immunosuppressive activities of Ibrutinib.Approved
IcatibantRoflumilast may increase the immunosuppressive activities of Icatibant.Approved
IdarubicinRoflumilast may increase the immunosuppressive activities of Idarubicin.Approved
IdelalisibRoflumilast may increase the immunosuppressive activities of Idelalisib.Approved
IfosfamideRoflumilast may increase the immunosuppressive activities of Ifosfamide.Approved
ImatinibRoflumilast may increase the immunosuppressive activities of Imatinib.Approved
ImiquimodRoflumilast may increase the immunosuppressive activities of Imiquimod.Approved, Investigational
InfliximabRoflumilast may increase the immunosuppressive activities of Infliximab.Approved
IrinotecanRoflumilast may increase the immunosuppressive activities of Irinotecan.Approved, Investigational
L-PhenylalanineRoflumilast may increase the immunosuppressive activities of L-Phenylalanine.Approved, Nutraceutical
LeflunomideRoflumilast may increase the immunosuppressive activities of Leflunomide.Approved, Investigational
LenalidomideRoflumilast may increase the immunosuppressive activities of Lenalidomide.Approved
LisofyllineRoflumilast may increase the immunosuppressive activities of Lisofylline.Investigational
LomustineRoflumilast may increase the immunosuppressive activities of Lomustine.Approved
LoxapineThe risk or severity of adverse effects can be increased when Roflumilast is combined with Loxapine.Approved
LumacaftorThe serum concentration of Roflumilast can be decreased when it is combined with Lumacaftor.Approved
Lx211Roflumilast may increase the immunosuppressive activities of Lx211.Investigational
MechlorethamineRoflumilast may increase the immunosuppressive activities of Mechlorethamine.Approved
MelphalanRoflumilast may increase the immunosuppressive activities of Melphalan.Approved
MepolizumabRoflumilast may increase the immunosuppressive activities of Mepolizumab.Approved, Investigational
MercaptopurineRoflumilast may increase the immunosuppressive activities of Mercaptopurine.Approved
MethotrexateRoflumilast may increase the immunosuppressive activities of Methotrexate.Approved
MethylprednisoloneRoflumilast may increase the immunosuppressive activities of Methylprednisolone.Approved, Vet Approved
MitomycinRoflumilast may increase the immunosuppressive activities of Mitomycin.Approved
MitotaneThe serum concentration of Roflumilast can be decreased when it is combined with Mitotane.Approved
MitoxantroneRoflumilast may increase the immunosuppressive activities of Mitoxantrone.Approved, Investigational
MizoribineRoflumilast may increase the immunosuppressive activities of Mizoribine.Investigational
MuromonabRoflumilast may increase the immunosuppressive activities of Muromonab.Approved, Investigational
Mycophenolate mofetilRoflumilast may increase the immunosuppressive activities of Mycophenolate mofetil.Approved, Investigational
Mycophenolic acidRoflumilast may increase the immunosuppressive activities of Mycophenolic acid.Approved
NafamostatRoflumilast may increase the immunosuppressive activities of Nafamostat.Investigational
NatalizumabRoflumilast may increase the immunosuppressive activities of Natalizumab.Approved, Investigational
NelarabineRoflumilast may increase the immunosuppressive activities of Nelarabine.Approved, Investigational
NevirapineThe serum concentration of Roflumilast can be decreased when it is combined with Nevirapine.Approved
NilotinibRoflumilast may increase the immunosuppressive activities of Nilotinib.Approved, Investigational
ObinutuzumabRoflumilast may increase the immunosuppressive activities of Obinutuzumab.Approved
OxaliplatinRoflumilast may increase the immunosuppressive activities of Oxaliplatin.Approved, Investigational
PaclitaxelRoflumilast may increase the immunosuppressive activities of Paclitaxel.Approved, Vet Approved
PalbociclibRoflumilast may increase the immunosuppressive activities of Palbociclib.Approved
PanobinostatRoflumilast may increase the immunosuppressive activities of Panobinostat.Approved, Investigational
PazopanibRoflumilast may increase the immunosuppressive activities of Pazopanib.Approved
PegaspargaseRoflumilast may increase the immunosuppressive activities of Pegaspargase.Approved, Investigational
PemetrexedRoflumilast may increase the immunosuppressive activities of Pemetrexed.Approved, Investigational
PentobarbitalThe serum concentration of Roflumilast can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PentostatinRoflumilast may increase the immunosuppressive activities of Pentostatin.Approved, Investigational
PhenobarbitalThe serum concentration of Roflumilast can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Roflumilast can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimecrolimusRoflumilast may increase the immunosuppressive activities of Pimecrolimus.Approved, Investigational
PirarubicinRoflumilast may increase the immunosuppressive activities of Pirarubicin.Investigational
PirfenidoneRoflumilast may increase the immunosuppressive activities of Pirfenidone.Investigational
PomalidomideRoflumilast may increase the immunosuppressive activities of Pomalidomide.Approved
PralatrexateRoflumilast may increase the immunosuppressive activities of Pralatrexate.Approved
PrednisoloneRoflumilast may increase the immunosuppressive activities of Prednisolone.Approved, Vet Approved
PrednisoneRoflumilast may increase the immunosuppressive activities of Prednisone.Approved, Vet Approved
PrimidoneThe serum concentration of Roflumilast can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcarbazineRoflumilast may increase the immunosuppressive activities of Procarbazine.Approved
RifabutinThe serum concentration of Roflumilast can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Roflumilast can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Roflumilast can be decreased when it is combined with Rifapentine.Approved
RilonaceptRoflumilast may increase the immunosuppressive activities of Rilonacept.Approved
RiociguatRoflumilast may increase the hypotensive activities of Riociguat.Approved
RituximabRoflumilast may increase the immunosuppressive activities of Rituximab.Approved
RuxolitinibRoflumilast may increase the immunosuppressive activities of Ruxolitinib.Approved
SecukinumabRoflumilast may increase the immunosuppressive activities of Secukinumab.Approved
SeocalcitolRoflumilast may increase the immunosuppressive activities of Seocalcitol.Experimental
SiltuximabRoflumilast may increase the immunosuppressive activities of Siltuximab.Approved
SirolimusRoflumilast may increase the immunosuppressive activities of Sirolimus.Approved, Investigational
SorafenibRoflumilast may increase the immunosuppressive activities of Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Roflumilast can be decreased when it is combined with St. John's Wort.Nutraceutical
SteproninRoflumilast may increase the immunosuppressive activities of Stepronin.Approved
StreptozocinRoflumilast may increase the immunosuppressive activities of Streptozocin.Approved
SunitinibRoflumilast may increase the immunosuppressive activities of Sunitinib.Approved, Investigational
TacrolimusRoflumilast may increase the immunosuppressive activities of Tacrolimus.Approved, Investigational
TemozolomideRoflumilast may increase the immunosuppressive activities of Temozolomide.Approved, Investigational
TemsirolimusRoflumilast may increase the immunosuppressive activities of Temsirolimus.Approved
TeniposideRoflumilast may increase the immunosuppressive activities of Teniposide.Approved
TepoxalinRoflumilast may increase the immunosuppressive activities of Tepoxalin.Vet Approved
TeriflunomideRoflumilast may increase the immunosuppressive activities of Teriflunomide.Approved
ThalidomideRoflumilast may increase the immunosuppressive activities of Thalidomide.Approved, Investigational, Withdrawn
ThiotepaRoflumilast may increase the immunosuppressive activities of Thiotepa.Approved
TioguanineRoflumilast may increase the immunosuppressive activities of Tioguanine.Approved
TocilizumabRoflumilast may increase the immunosuppressive activities of Tocilizumab.Approved
TofacitinibRoflumilast may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TopotecanRoflumilast may increase the immunosuppressive activities of Topotecan.Approved, Investigational
TositumomabRoflumilast may increase the immunosuppressive activities of Tositumomab.Approved
TrabectedinRoflumilast may increase the immunosuppressive activities of Trabectedin.Approved, Investigational
Trastuzumab emtansineRoflumilast may increase the immunosuppressive activities of Trastuzumab emtansine.Approved
TretinoinRoflumilast may increase the immunosuppressive activities of Tretinoin.Approved, Investigational, Nutraceutical
TriamcinoloneRoflumilast may increase the immunosuppressive activities of Triamcinolone.Approved, Vet Approved
TrofosfamideRoflumilast may increase the immunosuppressive activities of Trofosfamide.Investigational
UstekinumabRoflumilast may increase the immunosuppressive activities of Ustekinumab.Approved, Investigational
VedolizumabRoflumilast may increase the immunosuppressive activities of Vedolizumab.Approved
VilanterolRoflumilast may increase the immunosuppressive activities of Vilanterol.Approved
VinblastineRoflumilast may increase the immunosuppressive activities of Vinblastine.Approved
VincristineRoflumilast may increase the immunosuppressive activities of Vincristine.Approved, Investigational
VindesineRoflumilast may increase the immunosuppressive activities of Vindesine.Approved
VinorelbineRoflumilast may increase the immunosuppressive activities of Vinorelbine.Approved, Investigational
Food InteractionsNot Available
References
Synthesis Reference

http://en.wikipedia.org/wiki/File:Roflumilast_syn.png

General References
  1. Meyers JA, Taverna J, Chaves J, Makkinje A, Lerner A: Phosphodiesterase 4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells. Clin Cancer Res. 2007 Aug 15;13(16):4920-7. [PubMed:17699872 ]
  2. Sanz MJ, Cortijo J, Taha MA, Cerda-Nicolas M, Schatton E, Burgbacher B, Klar J, Tenor H, Schudt C, Issekutz AC, Hatzelmann A, Morcillo EJ: Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br J Pharmacol. 2007 Oct;152(4):481-92. Epub 2007 Aug 20. [PubMed:17704822 ]
  3. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [PubMed:17726343 ]
  4. Chong J, Poole P, Leung B, Black PN: Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011 May 11;(5):CD002309. doi: 10.1002/14651858.CD002309.pub3. [PubMed:21563134 ]
  5. Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker D, Bethke TD, Hiemstra PS, Rabe KF: Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. Epub 2007 Jun 15. [PubMed:17573446 ]
  6. Thappali SR, Varanasi KV, Veeraraghavan S, Vakkalanka SK, Mukkanti K: Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study. J Mass Spectrom. 2012 Dec;47(12):1612-9. doi: 10.1002/jms.3103. [PubMed:23280750 ]
External Links
ATC CodesR03DX07
AHFS Codes
  • 48:32
PDB Entries
FDA labelDownload (255 KB)
MSDSDownload (569 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9874
Caco-2 permeable+0.5235
P-glycoprotein substrateNon-substrate0.7295
P-glycoprotein inhibitor INon-inhibitor0.5775
P-glycoprotein inhibitor IINon-inhibitor0.622
Renal organic cation transporterNon-inhibitor0.8057
CYP450 2C9 substrateNon-substrate0.8082
CYP450 2D6 substrateNon-substrate0.7705
CYP450 3A4 substrateSubstrate0.5821
CYP450 1A2 substrateInhibitor0.7732
CYP450 2C9 inhibitorInhibitor0.5686
CYP450 2D6 inhibitorNon-inhibitor0.7204
CYP450 2C19 inhibitorInhibitor0.7813
CYP450 3A4 inhibitorInhibitor0.6242
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8602
Ames testNon AMES toxic0.5216
CarcinogenicityNon-carcinogens0.8843
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3522 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9704
hERG inhibition (predictor II)Non-inhibitor0.6336
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral500 ug/1
TabletOral500 mcg
Tablet, film coatedOral500 μg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5712298 No2000-01-272020-01-27Us
US8431154 No2003-02-192023-02-19Us
US8536206 No2004-03-082024-03-08Us
US8604064 No2004-03-082024-03-08Us
US8618142 No2004-03-082024-03-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point159.7Not Available
water solubilityinsoluble (0.52-0.56 mg/L at 22°C)Not Available
pKa8.74Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0062 mg/mLALOGPS
logP4.47ALOGPS
logP4.45ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)8.18ChemAxon
pKa (Strongest Basic)2.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.45 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity93.92 m3·mol-1ChemAxon
Polarizability35.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (81 KB)
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-arylamides. These are organic compounds that contain a carboxamide group that is N-linked to a aryl group. They have the generic structure RC(=O)N(R')H, R = organyl group and R'= aryl group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassN-arylamides
Sub ClassNot Available
Direct ParentN-arylamides
Alternative Parents
Substituents
  • N-arylamide
  • Benzoic acid or derivatives
  • Benzamide
  • Polyhalopyridine
  • Phenol ether
  • Benzoyl
  • Aminopyridine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Halomethane
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ubiquitin protein ligase binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4D
Uniprot ID:
Q08499
Molecular Weight:
91114.1 Da
References
  1. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [PubMed:17726343 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
References
  1. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [PubMed:17726343 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Molecular Weight:
83342.695 Da
References
  1. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [PubMed:17726343 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4C
Uniprot ID:
Q08493
Molecular Weight:
79900.795 Da
References
  1. Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [PubMed:17726343 ]
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Drug created on June 13, 2005 07:24 / Updated on December 03, 2016 02:45