Details of the Drug

General Information of Drug (ID: DMTWS9E)

Drug Name
Apremilast
Synonyms Apremilast (USAN); CC-10004; N-[2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methylsulfonyl-ethyl]-1,3-dioxo-isoindol-4-yl]acetamide
Indication
Disease Entry ICD 11 Status REF
Psoriasis vulgaris EA90 Approved [1]
Psoriatic arthritis FA21 Approved [2]
Affected Organisms
Humans and other mammals
ATC Code
L04AA32: Apremilast
L04AA: Selective immunosuppressants
L04A: IMMUNOSUPPRESSANTS
L04: IMMUNOSUPPRESSANTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 460.5
Logarithm of the Partition Coefficient (xlogp) 1.8
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 584 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2.5 h [3]
Bioavailability
The bioavailability of drug is 73% [3]
Clearance
The clearance of drug is 10 L/h [4]
Elimination
Only 3% and 7% of an apremilast dose are detected in the urine and feces as unchanged drug, respectively [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 6 - 9 hours [5]
Metabolism
The drug is metabolized via oxidation, hydrolysis, in addition to conjugation [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.32% [7]
Vd
The volume of distribution (Vd) of drug is 87 L [4]
Chemical Identifiers
Formula
C22H24N2O7S
IUPAC Name
N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide
Canonical SMILES
CCOC1=C(C=CC(=C1)[C@@H](CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
InChI
InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1
InChIKey
IMOZEMNVLZVGJZ-QGZVFWFLSA-N
Cross-matching ID
PubChem CID
11561674
ChEBI ID
CHEBI:78540
CAS Number
608141-41-9
UNII
UP7QBP99PN
DrugBank ID
DB05676
TTD ID
D07ESC
VARIDT ID
DR01264
INTEDE ID
DR0124
ACDINA ID
D00041
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Inhibitor [8]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Inhibitor [8]
Phosphodiesterase 4 (PDE4) TTV5CGO NOUNIPROTAC Inhibitor [9]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [11]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Substrate [12]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Psoriasis vulgaris
ICD Disease Classification EA90
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 4 (CDK4) DTT CDK4 3.30E-72 0.65 2.39
P-glycoprotein 1 (ABCB1) DTP P-GP 3.12E-33 -8.30E-01 -1.04E+00
Cytochrome P450 2A6 (CYP2A6) DME CYP2A6 5.48E-01 -5.89E-02 -1.77E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 5.52E-19 -2.25E-01 -5.53E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 5.59E-39 -3.76E-01 -1.64E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Apremilast (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Ivosidenib DM8S6T7 Moderate Increased metabolism of Apremilast caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [13]
Arn-509 DMT81LZ Major Increased metabolism of Apremilast caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [13]
Gilteritinib DMTI0ZO Moderate Decreased clearance of Apremilast due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [14]
Erdafitinib DMI782S Moderate Decreased clearance of Apremilast due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [15]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Apremilast caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [13]
Tucatinib DMBESUA Moderate Decreased clearance of Apremilast due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [16]
PF-04449913 DMSB068 Moderate Decreased clearance of Apremilast due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [17]
Lumacaftor DMCLWDJ Major Increased metabolism of Apremilast caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [18]
Cenobamate DM8KLU9 Moderate Increased metabolism of Apremilast caused by Cenobamate mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Rufinamide DMWE60C Moderate Increased metabolism of Apremilast caused by Rufinamide mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Apremilast caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [13]
Tazemetostat DMWP1BH Moderate Increased metabolism of Apremilast caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [13]
Ripretinib DM958QB Moderate Decreased clearance of Apremilast due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [14]
GS-5885 DMSL3DX Moderate Decreased clearance of Apremilast due to the transporter inhibition by GS-5885. Hepatitis virus infection [1E50-1E51] [19]
Etravirine DMGV8QU Moderate Increased metabolism of Apremilast caused by Etravirine mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [13]
Lesinurad DMUR64T Moderate Increased metabolism of Apremilast caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [13]
Brigatinib DM7W94S Moderate Increased metabolism of Apremilast caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [13]
PF-06463922 DMKM7EW Moderate Increased metabolism of Apremilast caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [13]
Vemurafenib DM62UG5 Moderate Increased metabolism of Apremilast caused by Vemurafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [13]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Apremilast caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [13]
Lasmiditan DMXLVDT Moderate Decreased clearance of Apremilast due to the transporter inhibition by Lasmiditan. Migraine [8A80] [20]
Abametapir DM2RX0I Moderate Decreased metabolism of Apremilast caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [21]
Lefamulin DME6G97 Moderate Decreased metabolism of Apremilast caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [22]
Enzalutamide DMGL19D Major Increased metabolism of Apremilast caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [13]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Apremilast caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [17]
Armodafinil DMGB035 Minor Increased metabolism of Apremilast caused by Armodafinil mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [23]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Apremilast caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [24]
Elagolix DMB2C0E Moderate Increased metabolism of Apremilast caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [13]
Betrixaban DM2C4RF Moderate Decreased clearance of Apremilast due to the transporter inhibition by Betrixaban. Venous thromboembolism [BD72] [25]
⏷ Show the Full List of 29 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
Carmellose sodium E00625 Not Available Disintegrant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Apremilast 30 mg tablet 30 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: 7372).
2 Apremilast FDA Label
3 FDA Approved Drug Products: Otezla (apremilast) tablets for oral use
4 Otezla product information
5 Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment option for nurse practitioners treating patients with psoriatic disease. J Am Assoc Nurse Pract. 2016 Dec;28(12):683-695. doi: 10.1002/2327-6924.12428. Epub 2016 Nov 21.
6 Chavan BB, Kalariya PD, Tiwari S, Nimbalkar RD, Garg P, Srinivas R, Talluri MVNK: Identification and characterization of vilazodone metabolites in rats and microsomes by ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry. Rapid Commun Mass Spectrom. 2017 Dec 15;31(23):1974-1984. doi: 10.1002/rcm.7982.
7 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8 Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
9 Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
10 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
11 Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: a novel treatment option for nurse practitioners treating patients with psoriatic disease. J Am Assoc Nurse Pract. 2016 Dec;28(12):683-695.
12 Apremilast (Otezla): a new oral treatment for adults with psoriasis and psoriatic arthritis. P T. 2015 Aug;40(8):495-500.
13 Product Information. Otezla (apremilast). Celgene Corporation, Summit, NJ.
14 Cerner Multum, Inc. "Australian Product Information.".
15 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
16 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
17 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18 Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
19 Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
20 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
21 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
22 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
23 Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
24 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
25 Product Information. Bevyxxa (betrixaban). Portola Pharmaceuticals, South San Francisco, CA.