Details of the Drug

General Information of Drug (ID: DMPGHY8)

Drug Name

Roflumilast

Synonyms

162401-32-3; DAXAS; Daliresp; 3-(CYCLOPROPYLMETHOXY)-N-(3,5-DICHLOROPYRIDIN-4-YL)-4-(DIFLUOROMETHOXY)BENZAMIDE; BY217; BYK20869; UNII-0P6C6ZOP5U; BY-217; Roflumilast (Daxas); B9302-107; 0P6C6ZOP5U; 3-(Cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)benzamide; Benzamide, 3-(cyclopropylmethoxy)-N-(3,5-dichloro-4-pyridinyl)-4-(difluoromethoxy)-; CHEMBL193240; CHEBI:47657; BYK-20869; ROF; Libertek; AK110425; 3-Cyclopropylmethoxy-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide; DAXAS; Roflumilast [USAN]; APTA-2217; Roflumilast (JAN/USAN/INN); 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-di-chloropyrid-4-yl)benzamide; Alogliptin/roflumilast

Indication

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Approved	[1], [2]
Type-2 diabetes	5A11	Phase 1	[3]
Chronic obstructive pulmonary disease	CA22	Withdrawn from market	[1], [4]
Atopic dermatitis	EA80	Discontinued in Phase 2	[1], [4]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

403.2

Topological Polar Surface Area (xlogp)

4.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.5-2 h [5]
Bioavailability: The bioavailability of drug is 80% [5]
Clearance: The clearance of drug is 9.6 L/h [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 17 hours [7]
Metabolism: The drug is metabolized via the CYP3A4 and CYP1A2 [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.01% [7]
Vd: The volume of distribution (Vd) of drug is 2.9 L/kg [6]

Chemical Identifiers

Formula: C17H14Cl2F2N2O3
IUPAC Name: 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
Canonical SMILES: C1CC1COC2=C(C=CC(=C2)C(=O)NC3=C(C=NC=C3Cl)Cl)OC(F)F
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)
InChIKey: MNDBXUUTURYVHR-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 449193
ChEBI ID: CHEBI:47657
CAS Number: 162401-32-3
DrugBank ID: DB01656
TTD ID: D0R4UW
INTEDE ID: DR1434
ACDINA ID: D00604

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 4 (PDE4)	TTV5CGO	NOUNIPROTAC	Modulator	[2], [8]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[9]
Cytochrome P450 1A2 (CYP1A2)_{Main DME}	DEJGDUW	CP1A2_HUMAN	Substrate	[9]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Roflumilast (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Midostaurin	DMI6E0R	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Midostaurin.	Acute myeloid leukaemia [2A60]	[36]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Roflumilast caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[37]
Siltuximab	DMGEATB	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Siltuximab.	Anemia [3A00-3A9Z]	[36]
Dupilumab	DMOAD2Y	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Dupilumab.	Atopic eczema [EA80]	[36]
Obeticholic acid	DM3Q1SM	Moderate	Decreased metabolism of Roflumilast caused by Obeticholic acid mediated inhibition of CYP450 enzyme.	Autoimmune liver disease [DB96]	[36]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Roflumilast caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[38]
Eribulin	DM1DX4Q	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Eribulin.	Breast cancer [2C60-2C6Y]	[36]
Talazoparib	DM1KS78	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Talazoparib.	Breast cancer [2C60-2C6Y]	[36]
Ixabepilone	DM2OZ3G	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ixabepilone.	Breast cancer [2C60-2C6Y]	[36]
LY2835219	DM93VBZ	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and LY2835219.	Breast cancer [2C60-2C6Y]	[36]
Pralatrexate	DMAO80I	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Pralatrexate.	Breast cancer [2C60-2C6Y]	[36]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Roflumilast caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[39]
Thiotepa	DMIZKOP	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Thiotepa.	Breast cancer [2C60-2C6Y]	[36]
Cabazitaxel	DMPAZHC	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Cabazitaxel.	Breast cancer [2C60-2C6Y]	[36]
Bosutinib	DMTI8YE	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Bosutinib.	Breast cancer [2C60-2C6Y]	[36]
Aflibercept	DMT3D5I	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Aflibercept.	Colorectal cancer [2B91]	[36]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Roflumilast caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[36]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Roflumilast caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[37]
Polatuzumab vedotin	DMF6Y0L	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Polatuzumab vedotin.	Diffuse large B-cell lymphoma [2A81]	[36]
Lisocabtagene maraleucel	DMP45ME	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Lisocabtagene maraleucel.	Diffuse large B-cell lymphoma [2A81]	[36]
Axicabtagene ciloleucel	DMYHN59	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Axicabtagene ciloleucel.	Diffuse large B-cell lymphoma [2A81]	[36]
Cenobamate	DMGOVHA	Moderate	Decreased metabolism of Roflumilast caused by Cenobamate mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[40]
Bay 80-6946	DMLOS5R	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Bay 80-6946.	Follicular lymphoma [2A80]	[36]
Avapritinib	DMK2GZX	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[36]
177Lu-DOTATATE	DMT8GVU	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[36]
Brentuximab vedotin	DMWLC57	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[36]
Teriflunomide	DMQ2FKJ	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[36]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Roflumilast caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[36]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Roflumilast caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[41]
Olaratumab	DMNYOIX	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Olaratumab.	Kaposi sarcoma [2B57]	[36]
Brigatinib	DM7W94S	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Brigatinib.	Lung cancer [2C25]	[36]
Lurbinectedin	DMEFRTZ	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Lurbinectedin.	Lung cancer [2C25]	[36]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Roflumilast caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[42]
Osimertinib	DMRJLAT	Moderate	Increased metabolism of Roflumilast caused by Osimertinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[43]
Capmatinib	DMYCXKL	Moderate	Decreased metabolism of Roflumilast caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[36]
Belimumab	DM3OBQF	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Belimumab.	Lupus erythematosus [4A40]	[36]
Inotuzumab ozogamicin	DMAC130	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[36]
Ofatumumab	DM295PR	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ofatumumab.	Mature B-cell leukaemia [2A82]	[36]
Obinutuzumab	DM3BVAE	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Obinutuzumab.	Mature B-cell leukaemia [2A82]	[36]
GDC-0199	DMH0QKA	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and GDC-0199.	Mature B-cell leukaemia [2A82]	[36]
IPI-145	DMWA24P	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and IPI-145.	Mature B-cell leukaemia [2A82]	[36]
Acalabrutinib	DM7GCVW	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[36]
Blinatumomab	DMGECIJ	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Blinatumomab.	Mature B-cell lymphoma [2A85]	[36]
Ibrutinib	DMHZCPO	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ibrutinib.	Mature B-cell lymphoma [2A85]	[36]
Tisagenlecleucel	DMM9BJD	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Tisagenlecleucel.	Mature B-cell lymphoma [2A85]	[36]
Ponatinib	DMYGJQO	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ponatinib.	Mature B-cell lymphoma [2A85]	[36]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Roflumilast caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[36]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Roflumilast caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[36]
Carfilzomib	DM48K0X	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Carfilzomib.	Multiple myeloma [2A83]	[36]
Panobinostat	DM58WKG	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Panobinostat.	Multiple myeloma [2A83]	[36]
Selinexor	DMBD4K3	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Selinexor.	Multiple myeloma [2A83]	[36]
Belantamab mafodotin	DMBT3AI	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Belantamab mafodotin.	Multiple myeloma [2A83]	[36]
Elotuzumab	DMEYHG9	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Elotuzumab.	Multiple myeloma [2A83]	[36]
Daratumumab	DMKCIUZ	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Daratumumab.	Multiple myeloma [2A83]	[36]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Tecfidera.	Multiple sclerosis [8A40]	[36]
Siponimod	DM2R86O	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Siponimod.	Multiple sclerosis [8A40]	[36]
Fingolimod	DM5JVAN	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Fingolimod.	Multiple sclerosis [8A40]	[36]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ocrelizumab.	Multiple sclerosis [8A40]	[36]
Deflazacort	DMV0RNS	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Deflazacort.	Muscular dystrophy [8C70]	[36]
Romidepsin	DMT5GNL	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Romidepsin.	Mycosis fungoides [2B01]	[36]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Roflumilast caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[36]
Nilotinib	DM7HXWT	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Nilotinib.	Myeloproliferative neoplasm [2A20]	[36]
Ruxolitinib	DM7Q98D	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[36]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[36]
Inebilizumab	DMI0RHA	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Inebilizumab.	Nervous system paraneoplastic/autoimmune disorder [8E4A]	[36]
Atezolizumab	DMMF8U0	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Atezolizumab.	Non-small cell lung cancer [2C25]	[36]
Olaparib	DM8QB1D	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Olaparib.	Ovarian cancer [2C73]	[36]
Rucaparib	DM9PVX8	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Rucaparib.	Ovarian cancer [2C73]	[36]
MK-4827	DMLYGH4	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and MK-4827.	Ovarian cancer [2C73]	[36]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Roflumilast caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[44]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Roflumilast caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[45]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Roflumilast caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[37]
Brodalumab	DMASDQ6	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Brodalumab.	Psoriasis [EA90]	[36]
Ustekinumab	DMHTYK3	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ustekinumab.	Psoriasis [EA90]	[36]
Tildrakizumab	DMLW9HG	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Tildrakizumab.	Psoriasis [EA90]	[36]
Risankizumab	DMM32GT	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Risankizumab.	Psoriasis [EA90]	[36]
Ixekizumab	DMXW92T	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Ixekizumab.	Psoriasis [EA90]	[36]
Temsirolimus	DMS104F	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Temsirolimus.	Renal cell carcinoma [2C90]	[36]
Upadacitinib	DM32B5U	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Upadacitinib.	Rheumatoid arthritis [FA20]	[36]
Baricitinib	DM4ONW5	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Baricitinib.	Rheumatoid arthritis [FA20]	[36]
Tocilizumab	DM7J6OR	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Tocilizumab.	Rheumatoid arthritis [FA20]	[36]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Canakinumab.	Rheumatoid arthritis [FA20]	[36]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Rilonacept.	Rheumatoid arthritis [FA20]	[36]
Golimumab	DMHZV7X	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Golimumab.	Rheumatoid arthritis [FA20]	[36]
Sarilumab	DMOGNXY	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Sarilumab.	Rheumatoid arthritis [FA20]	[36]
Mogamulizumab	DMISH0Z	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Mogamulizumab.	Sezary syndrome [2B02]	[36]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Roflumilast caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[36]
Trabectedin	DMG3Y89	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[36]
LEE011	DMMX75K	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[36]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Roflumilast caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[36]
Pomalidomide	DMTGBAX	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Pomalidomide.	Systemic sclerosis [4A42]	[36]
Plicamycin	DM7C8YV	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Plicamycin.	Testicular cancer [2C80]	[36]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Roflumilast caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[46]
Belatacept	DMXLYQF	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Belatacept.	Transplant rejection [NE84]	[36]
Durvalumab	DM4PVDY	Moderate	Additive immunosuppressive effects by the combination of Roflumilast and Durvalumab.	Ureteral cancer [2C92]	[36]
-----------


⏷ Show the Full List of 95 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
--------------------

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Roflumilast 0.5 mg tablet	0.5 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6962).
2	2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
3	ClinicalTrials.gov (NCT01664624) Roflumilast Plus Alogliptin Proof-of-Mechanism Study in Type2 Diabetes. U.S. National Institutes of Health.
4	Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2009 Mar;14(1):165-79.
5	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
7	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8	Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease.Br J Pharmacol.2011 May;163(1):53-67.
9	Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2011 Apr;51(4):586-93.
10	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
11	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
12	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
13	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
14	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
15	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
16	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
17	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
18	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
19	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
20	Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
21	Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
22	Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
23	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
24	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
25	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
26	Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
27	Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
28	Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
29	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
30	Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
31	2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
32	Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
33	Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
34	Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
35	Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
36	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
37	Nassr N, Huennemeyer A, Herzog R, et al. "Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects." Br J Clin Pharmacol 68 (2009): 580-7. [PMID: 19843061]
38	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
39	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
40	Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
41	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
42	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
43	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
44	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
45	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
46	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.