Upadacitinib

Identification

Summary

Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor used in the treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, and severe atopic dermatitis, including in patients who did not respond well to other therapies.

Brand Names
Rinvoq
Generic Name
Upadacitinib
DrugBank Accession Number
DB15091
Background

Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression. Rheumatoid arthritis is a chronic autoimmune inflammatory disease affecting the peripheral joints. It is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage damage and bone destruction, leading to co-morbidities.4 Despite a variety of therapeutic agents available for treatment, up to 40% of the patients do not respond to current therapies, including biological therapies.6 The etiology of the disease is mostly unknown; however, the role of JAK as a driver of immune-mediated conditions was discovered, leading to the use of JAK as therapeutic targets for rheumatoid arthritis.5 To reduce dose-related toxicity (as seen with some pan-JAK inhibitors) without significantly affecting efficacy, more selective JAK1 inhibitors, upadacitinib and filgotinib, were developed.4

The FDA approved upadacitinib in August 2019 and it is used for the treatment of active rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.9 In December 2019, it was additionally approved by the European Commission and Health Canada.10,15 Upadacitinib is marketed under the brand name RINVOQ for oral administration.9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 380.375
Monoisotopic: 380.157243745
Chemical Formula
C17H19F3N6O
Synonyms
  • Upadacitinib
External IDs
  • ABT 494
  • ABT-494

Pharmacology

Indication

Upadacitinib is indicated for the treatment of moderately to severely active rheumatoid arthritis or active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as TNF blockers.9,14 In Europe, upadacitinib may be used as monotherapy or in combination with methotrexate for rheumatoid or psoriatic arthritis.14

Upadacitinib is indicated for use in patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is inadequately controlled with other systemic therapies or when other therapies are inadvisable.9,14

Upadacitinib is indicated for the treatment of active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have an inadequate response to conventional therapy.9,14 It is also indicated to treat non-radiographic axial spondyloarthritis with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.9

Upadacitinib is also indicated to treat moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent,14 such as to one or more TNF blockers.9

Upadacitinib is indicated to treat moderately to severely active Crohn’s disease in adults who have had an inadequate response or intolerance to one or more TNF blockers.17,14

Combining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.9

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAnkylosing spondylitis (as)••••••••••••••••••••••••••• •••••••• •• •••••••••••• •••••••••••••• •••••••• •••••••
Used in combination to manageAnkylosing spondylitis (as)••••••••••••••••••••••••••• •••••••• •• ••••••••••• •• ••••••••••••• •••••••• •••••••
Management ofModerately to severely active crohn's disease•••••••••••••••••••••••• •• ••••••••• •••••••••••••• •••••••• •••••••
Used in combination to manageModerately to severely active rheumatoid arthritisRegimen in combination with: Methotrexate (DB00563)••••••••••••••••••••••••••• •••••••• •• ••••••••••• •• ••••••••••••• •••••••• •••••••
Used in combination to manageModerately to severely active rheumatoid arthritis•••••••••••••••••••••••• •••••••• •••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Upadacitinib is a DMARD that works by inhibiting the Janus Kinases (JAKs), which are essential downstream cell signalling mediators of pro-inflammatory cytokines. It is believed that these pro-inflammatory cytokines play a role in many autoimmune inflammatory conditions, such as rheumatoid arthritis.6 In clinical trials, upadacitinib decreased the activity of pro-inflammatory interleukins, transiently increased the levels of lymphocytes, and insignificantly decreased the levels of immunoglobulins from the baseline.9

Mechanism of action

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves the interplay of several mediators, including the immune cells (mainly T- and B-lymphocytes) and pro-inflammatory cytokines, such as the tumour necrosis factor (TNF), transforming growth factor (TGF), and interleukin 6 (IL-6).4 The Janus Kinase (JAK) family plays an essential role in the normal physiological functions (such as erythropoiesis), but also the signalling of pro-inflammatory cytokines that are implicated in many immune-mediated diseases.5 The JAK family consists of four isoforms (JAK1, JAK2, JAK3, and Tyrosine Kinase 2) that each interacts with different cytokine receptors and uniquely associates with the intracellular domains of Type I/II cytokine receptors.5 JAK1 is primarily involved in the signalling transduction pathways of IL-6, IFN and the common γ -chain cytokines, including IL-2 and IL-15.8 IL-6 has been closely studied in particular, as it is a major cytokine involved in B- and T-cell differentiation and the acute phase response in inflammation.7

Upon interaction of cytokines with their cytokine receptors, the JAKs mediate the JAK-STAT signal transduction pathway in response to receptor activation. JAKs are tyrosine kinases that cause phosphorylation of several proteins, including cytokine receptors and JAKs themselves. Phosphorylation of JAKs promotes the phosphorylation and activation of the signalling molecules called STATs, leading to their nuclear translocation, binding to DNA promoters, and target gene transcription. JAK1-mediated signalling pathways ultimately promote pro-inflammatory events, such as increased proliferation and survival of immune cells, T cell differentiation, and macrophage activation.5 Upadacitinib is a selective JAK1 inhibitor that has a negligible effect on JAK3, leading to an improved drug safety profile.4 Upadacitinib blocks the cellular processes that contribute to the inflammatory conditions in rheumatoid arthritis. In human leukocytes cellular assays, upadacitinib inhibited JAK1/3-induced phosphorylation of STAT3/5 mediated by IL-6/7.9

TargetActionsOrganism
ATyrosine-protein kinase JAK1
inhibitor
Humans
Absorption

Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range. Following oral administration, the median time to reach Cmax (Tmax) ranges from 2 to 4 hours. The steady-state plasma concentrations of upadacitinib are reached within 4 days following multiple once-daily administrations, with minimal accumulation.9 Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation.3

Volume of distribution

The volume of distribution of upadacitinib in a patient with rheumatoid arthritis and a body weight of 74 kg is estimated to be 224 L following oral administration of an extended-release formula.11 In a pharmacokinetic study consisting of healthy volunteers receiving the extended-release formulation, the steady-state volume of distribution was 294 L.1 Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.9

Protein binding

Upadacitinib is 52% bound to human plasma proteins.9

Metabolism

Upadacitinib predominantly undergoes CYP3A4-mediated metabolism;9 however, upadacitinib is a nonsensitive substrate of CYP3A4.3 It is also metabolized by CYP2D6 to a lesser extent.9 In a human radio-labelled study, about 79% of the total plasma radioactivity accounted for the parent drug, and about 13% of the total plasma radioactivity accounted for the main metabolite produced from mono-oxidation, followed by glucuronidation.9 There are no known active metabolites of upadacitinib.11

Route of elimination

Following administration of a single radio-labelled dose from the immediate-release formulation, approximately 53% of the total dose was excreted in the feces where 38% of the excreted dose was an unchanged parent drug. About 43% of the total dose was excreted in the urine, where 24% of that dose was in the unchanged parent drug form.11 Approximately 34% of the total dose of upadacitinib dose was excreted as metabolites.9

Half-life

The mean terminal elimination half-life of upadacitinib ranged from 8 to 14 hours following administration of the extended-release formulation.9,11 In clinical trials, approximately 90% of upadacitinib in the systemic circulation was eliminated within 24 hours of dosing.9

Clearance

The apparent oral clearance of upadacitinib in healthy volunteers receiving the extended-release formulation was 53.7 L/h.1

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

There is limited clinical information on the overdose from upacitinib: in clinical trials, once-daily administration of 60 mg in extended-release formulations were well tolerated. In case of an overdose, it is recommended that the patient is monitored for signs and symptoms of adverse reactions and treated with appropriate symptomatic treatment.9

The oral LD50 in rats is 14500 mg/kg.12

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Upadacitinib can be increased when it is combined with Abametapir.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Upadacitinib.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Upadacitinib.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Upadacitinib.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Upadacitinib.
Food Interactions
  • Avoid grapefruit products. Upadacitinib exposure is increased when a strong CYP3A4 inhibitor such as grapefruit is used, which may increase the risk for drug-related adverse events.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of upadacitinib.
  • Take with or without food. Food does not significantly affect drug concentrations.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Upadacitinib hemihydrateNEW4DV02U5Not AvailableGJMQTRCDSIQEFK-SCDRJROZSA-N
Upadacitinib tartrate7KCW9IQM021607431-21-9LATZVDXOTDYECD-UFTFXDLESA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RinvoqTablet, extended release45 mgOralAbbvie2023-09-07Not applicableCanada flag
RinvoqTablet, extended release30 mgOralAbb Vie Deutschland Gmb H & Co. Kg2022-05-04Not applicableEU flag
RinvoqTablet, extended release30 mgOralAbbvie2021-10-28Not applicableCanada flag
RinvoqTablet, extended release15 mgOralAbb Vie Deutschland Gmb H & Co. Kg2021-02-10Not applicableEU flag
RinvoqTablet, extended release45 mgOralAbb Vie Deutschland Gmb H & Co. Kg2023-02-08Not applicableEU flag

Categories

ATC Codes
L04AA44 — Upadacitinib
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4RA0KN46E0
CAS number
1310726-60-3
InChI Key
WYQFJHHDOKWSHR-MNOVXSKESA-N
InChI
InChI=1S/C17H19F3N6O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27)/t10-,11+/m1/s1
IUPAC Name
(3S,4R)-3-ethyl-4-{1,5,7,10-tetraazatricyclo[7.3.0.0^{2,6}]dodeca-2(6),3,7,9,11-pentaen-12-yl}-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide
SMILES
CC[C@@H]1CN(C[C@@H]1C1=CN=C2C=NC3=C(C=CN3)N12)C(=O)NCC(F)(F)F

References

General References
  1. Klunder B, Mittapalli RK, Mohamed MF, Friedel A, Noertersheuser P, Othman AA: Population Pharmacokinetics of Upadacitinib Using the Immediate-Release and Extended-Release Formulations in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I-III Clinical Trials. Clin Pharmacokinet. 2019 Aug;58(8):1045-1058. doi: 10.1007/s40262-019-00739-3. [Article]
  2. Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, Camp HS, Padley RJ, George JS, Hyland D, Rosebraugh M, Wishart N, Olson L, Long AJ: In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018 Aug 28;2:23. doi: 10.1186/s41927-018-0031-x. eCollection 2018. [Article]
  3. Mohamed MF, Zeng J, Marroum PJ, Song IH, Othman AA: Pharmacokinetics of Upadacitinib With the Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials. Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462. Epub 2018 Apr 24. [Article]
  4. Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG: Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs Context. 2019 Oct 24;8:212595. doi: 10.7573/dic.212595. eCollection 2019. [Article]
  5. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec 28;17(1):78. doi: 10.1038/nrd.2017.267. [Article]
  6. Rivellese F, Lobasso A, Barbieri L, Liccardo B, de Paulis A, Rossi FW: Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors. Curr Med Chem. 2019;26(16):2823-2843. doi: 10.2174/0929867325666180209145243. [Article]
  7. Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR, et al.: A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995 Apr 3;14(7):1421-9. [Article]
  8. Choy EH: Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology (Oxford). 2019 Jun 1;58(6):953-962. doi: 10.1093/rheumatology/key339. [Article]
  9. FDA Approved Drug Products: RINVOQ (upadacitinib) extended-release tablets, for oral use [Link]
  10. AbbVie Receives European Commission Approval of RINVOQ™ (upadacitinib) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis [Link]
  11. FDA: Upadacitinib Summary Review [Link]
  12. EZSolution: Upadacitinib MSDS [Link]
  13. FDA: Upadacitinib Clinical Pharmacology and Biopharmaceutics Review(s) [Link]
  14. EMA Product Information: RINVOQ (upadacitinib) extended-release tablets [Link]
  15. Health Canada Approved Drug Products: Rinvoq (upadacitinib) extended-release tablets for oral use (October 2023) [Link]
  16. FDA Approved Drug Products: RINVOQ (upadacitinib) extended-release tablets, for oral use (April 2023) [Link]
  17. FDA Approved Drug Products: RINVOQ (upadacitinib) extended-release tablets, for oral use (May 2023) [Link]
ChemSpider
44210449
BindingDB
50503287
RxNav
2196092
ChEMBL
CHEMBL3622821
Wikipedia
Upadacitinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAtopic Dermatitis1
4Not Yet RecruitingTreatmentRheumatoid Arthritis1
4RecruitingPreventionCoronavirus Disease 2019 (COVID‑19) / Psoriatic Arthritis / Rheumatoid Arthritis / Spondylarthritis1
4RecruitingTreatmentAcute Ulcerative Colitis1
3Active Not RecruitingTreatmentAtopic Dermatitis4

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral15.400 mg
Tablet, extended releaseOral15 mg
Tablet, extended releaseOral15 mg/1
Tablet, extended releaseOral30 mg/1
Tablet, extended releaseOral30 mg
Tablet, extended releaseOral45 mg
Tablet, extended releaseOral45 mg/1
TabletOral15 mg
Tablet, film coated, extended releaseOral15 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8962629No2015-02-242031-01-15US flag
USRE47221No2019-02-052030-12-01US flag
US9951080No2018-04-242036-10-17US flag
US9963459No2018-05-082036-10-17US flag
US10519164No2019-12-312036-10-17US flag
US10597400No2020-03-242036-10-17US flag
US10981923No2021-04-202036-10-17US flag
US10981924No2021-04-202036-10-17US flag
US11198697No2021-12-142036-10-17US flag
US11186584No2021-11-302036-10-17US flag
US10550126No2020-02-042036-10-17US flag
US10995095No2021-05-042036-10-17US flag
US10730883No2020-08-042036-10-17US flag
US10344036No2019-07-092036-10-17US flag
US10202393No2019-02-122036-10-17US flag
US11365198No2016-10-172036-10-17US flag
US11512092No2016-10-172036-10-17US flag
US11524964No2016-10-172036-10-17US flag
US11535624No2016-10-172036-10-17US flag
US11535625No2016-10-172036-10-17US flag
US11535626No2016-10-172036-10-17US flag
US11607411No2018-03-092038-03-09US flag
US11661425No2016-10-172036-10-17US flag
US11564922No2018-03-092038-03-09US flag
US11680069No2016-10-172036-10-17US flag
US11718627No2016-10-172036-10-17US flag
US11773106No2016-10-172036-10-17US flag
US11767326No2016-10-172036-10-17US flag
US11773105No2016-10-172036-10-17US flag
US11795175No2016-10-172036-10-17US flag
US11780848No2016-10-172036-10-17US flag
US11787815No2016-10-172036-10-17US flag
US11780847No2016-10-172036-10-17US flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)16-19MSDS
boiling point (°C)189MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0707 mg/mLALOGPS
logP2.57ALOGPS
logP0.85Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)13.99Chemaxon
pKa (Strongest Basic)4.11Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area78.32 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity93.03 m3·mol-1Chemaxon
Polarizability36.09 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0009000000-26f010bbf61856f19049
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-056r-0059000000-e385e1406b634e6e600e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0190000000-cc2338f5d743f26d5c59
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-1069000000-f8251949a60e4219c77e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pbi-1390000000-a7a6ddaac25c9d3e6590
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0490000000-0dd94db82b2cab4b42a0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Gene Name
JAK1
Uniprot ID
P23458
Uniprot Name
Tyrosine-protein kinase JAK1
Molecular Weight
133275.995 Da
References
  1. Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG: Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs Context. 2019 Oct 24;8:212595. doi: 10.7573/dic.212595. eCollection 2019. [Article]
  2. Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, Camp HS, Padley RJ, George JS, Hyland D, Rosebraugh M, Wishart N, Olson L, Long AJ: In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018 Aug 28;2:23. doi: 10.1186/s41927-018-0031-x. eCollection 2018. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Klunder B, Mittapalli RK, Mohamed MF, Friedel A, Noertersheuser P, Othman AA: Population Pharmacokinetics of Upadacitinib Using the Immediate-Release and Extended-Release Formulations in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I-III Clinical Trials. Clin Pharmacokinet. 2019 Aug;58(8):1045-1058. doi: 10.1007/s40262-019-00739-3. [Article]
  2. Mohamed MF, Zeng J, Marroum PJ, Song IH, Othman AA: Pharmacokinetics of Upadacitinib With the Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials. Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462. Epub 2018 Apr 24. [Article]
  3. FDA Approved Drug Products: RINVOQ (upadacitinib) extended-release tablets, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Klunder B, Mittapalli RK, Mohamed MF, Friedel A, Noertersheuser P, Othman AA: Population Pharmacokinetics of Upadacitinib Using the Immediate-Release and Extended-Release Formulations in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I-III Clinical Trials. Clin Pharmacokinet. 2019 Aug;58(8):1045-1058. doi: 10.1007/s40262-019-00739-3. [Article]
  2. Mohamed MF, Zeng J, Marroum PJ, Song IH, Othman AA: Pharmacokinetics of Upadacitinib With the Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials. Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462. Epub 2018 Apr 24. [Article]
  3. FDA Approved Drug Products: RINVOQ (upadacitinib) extended-release tablets, for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
Upadacitinib is a weak inhibitor of P-gp, but no interactions are expected at therapeutic levels with 15 mg QD dosing regimen. Modulation of P- gp transporters is expected to have minor effect on upadacitinib exposures.
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA: Upadacitinib Clinical Pharmacology and Biopharmaceutics Review(s) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
Upadacitinib is a weak inhibitor of BCRP, but no interactions are expected at therapeutic levels with 15 mg QD dosing regimen. Modulation of BCRP transporters is expected to have minor effect on upadacitinib exposures.
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA: Upadacitinib Clinical Pharmacology and Biopharmaceutics Review(s) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Upadacitinib is a weak inhibitor of OATP1B1, but no interactions are expected at therapeutic levels with 15 mg QD dosing regimen.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA: Upadacitinib Clinical Pharmacology and Biopharmaceutics Review(s) [Link]

Drug created at May 20, 2019 14:49 / Updated at December 14, 2023 19:14