| 词条 |
Oclacitinib |
| 释义 |
- Uses
- Contraindications
- Side effects
- Pharmacodynamics Mechanism of action Pharmacokinetics
- References
- External links
{{Drugbox
| IUPAC_name = N-Methyl{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin- 4-yl)amino]cyclohexyl}methanesulfonamide
| image = Oclacitinib.svg
| width =
| image2 =Apoquel bottle.jpg
| tradename = Apoquel
| Drugs.com ={{Drugs.com|vet|apoquel}}
| class = JAK inhibitor
| licence_US =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status = Rx-only
| routes_of_administration = By mouth (tablets)
| bioavailability = 89%> |
| Receptor | Mean IC50 (nM) |
|---|
| JAK1 | 10 |
| JAK2 | 18 |
| JAK3 | 99 |
| TYK2 | 84 |
This causes the inhibition of pro-inflammatory and pruritogenic (itch-causing) cytokines that depend on JAK1 and JAK3, which include IL-2, IL-4, IL-6, IL-13, and IL-31[1][10][11] (TSLP, another pruritogenic cytokine that uses JAKs, has also been found to be inhibited).[19][20] IL-31 is a key cytokine at the pruritogenic receptors at neurons near the skin, and also induces peripheral blood mononuclear cells and keratinocytes to release pro-inflammatory cytokines.[15] Suppression of IL-4 and IL-13 causes a decrease of Th2-cell differentiation, which plays a role in atopic dermatitis.[18] Oclacitinib's relatively little effect on JAK2 prevent it from suppressing hematopoiesis or the innate immune response.[5][11]
Oclacitinib inhibits JAK, not the pruritogenic cytokines themselves; studies in mice showed than suddenly stopping the medication caused an increase in itchiness caused by a rebound effect, where more cytokines were produced to overcome lack of response by JAK.[20]
Pharmacokinetics
Oclacitinib is absorbed well when taken orally; it takes less than an hour to reach peak plasma concentration and has a bioavailability of 89%.[1] In most dogs, pruritus begins to subside within four hours and is completely gone within 24.[13] Oclacitinib is cleared mostly by being metabolized in the liver, though there is some renal and biliary clearance as well.[1]
References
1. ^1 2 3 4 5 -->| protein_bound = 66.3–69.7%| metabolism = Liver| elimination_half-life = 3.1–5.2 hours[{{cite web|title=Apoquel (oclacitinib maleate tablet) Full Prescribing Information|url=https://www.zoetisus.com/bmst-minisite-apoquel/documents/finalapoquel_pi_8_5x11.pdf|publisher=Zoetis Inc. Kalamazoo, MI 49007|accessdate=23 February 2017}}]
2. ^-->| CAS_number = 1208319-26-9| PubChem = 44631938| ChemSpiderID = 28528036| UNII = 99GS5XTB51| KEGG = D10141| ChEMBL = 2103874| ATCvet = yes| ATC_prefix = D11| ATC_suffix = AH90| synonyms = PF-03394197| chemical_formula =| C=15 | H=23 | N=5 | O=2 | S=1| molecular_weight =| smiles = CNS(=O)(=O)C[C@@H]1CC[C@H](CC1)N(C)c2[nH]cnc3nccc23| StdInChI = 1S/C15H23N5O2S/c1-16-23(21,22)9-11-3-5-12(6-4-11)20(2)15-13-7-8-17-14(13)18-10-19-15/h7-8,10-12,16H,3-6,9H2,1-2H3,(H,17,18,19)/t11-,12-| StdInChIKey = HJWLJNBZVZDLAQ-HAQNSBGRSA-N}}Oclacitinib (brand name Apoquel) is a veterinary medication used in the control of atopic dermatitis and pruritus from allergic dermatitis in dogs at least 12 months of age.[{{cite web|title=Apoquel (oclacitinib maleate tablet) Full Prescribing Information|url=https://www.zoetisus.com/bmst-minisite-apoquel/documents/finalapoquel_pi_8_5x11.pdf|publisher=Zoetis Inc. Kalamazoo, MI 49007|accessdate=23 February 2017}}]
3. ^1 {{cite web|title=FDA Approves Apoquel (oclacitinib tablet) to Control Itch and Inflammation in Allergic Dogs|url=http://news.zoetis.com/press-release/companion-animals/fda-approves-apoquel-oclacitinib-tablet-control-itch-and-inflammatio|publisher=Zoetis|accessdate=23 February 2017|date=16 May 2013}}
4. ^1 2 {{cite journal|last1=Gonzales|first1=AJ|last2=Bowman|first2=JW|last3=Fici|first3=GJ|last4=Zhang|first4=M|last5=Mann|first5=DW|last6=Mitton-Fry|first6=M|title=Oclacitinib (Apoquel®) Is a Novel Janus Kinase Inhibitor with Activity Against Cytokines Involved in Allergy|journal=Journal of Veterinary Pharmacology and Therapeutics|date=August 2014|volume=37|issue=4|pages=317–24|doi=10.1111/jvp.12101|pmid=24495176|pmc=4265276}}
5. ^1 {{cite book|url=https://books.google.com/books?id=Jl0SCAAAQBAJ&pg=PA363|title=Pharmacology of Itch|last1=Cowan|first1=Alan|last2=Yosipovitch|first2=Gil|publisher=Springer|year=2015|isbn=978-3-662-44605-8|pages=363–364|ref=harv}}
6. ^1 2 {{cite book|url=https://books.google.com/books?id=xT_UDAAAQBAJ&pg=PA190|title=Small Animal Dermatology - E-Book: A Color Atlas and Therapeutic Guide|last1=Hnilica|first1=Keith A.|last2=Patterson|first2=Adam P.|publisher=Elsevier Health Sciences|year=2016|isbn=978-0-323-39067-5|page=190|ref=harv}}
7. ^{{cite book|url=https://books.google.com/books?id=NmziBQAAQBAJ&pg=PA1765|title=Clinical Veterinary Advisor - E-Book: Dogs and Cats|last=Cote|first=Etienne|publisher=Elsevier Health Sciences|year=2014|isbn=978-0-323-24074-1|page=1765|ref=harv}}
8. ^1 2 3 4 5 6 7 8 {{cite journal|last1=Falk|first1=Elisabeth|last2=Ferrer|first2=Lluís|date=December 2015|title=Oclacitinib|url=https://www.cliniciansbrief.com/sites/default/files/attachments/MEDS_Oclacitinib.pdf|journal=Clinician's Brief|ref=harv}}
9. ^{{cite web|url=https://www.merckvetmanual.com/integumentary-system/atopic-dermatitis/canine-atopic-dermatitis|title=Canine Atopic Dermatitis|last=Moriello|first=Karen|work=Merck Veterinary Manual|accessdate=27 February 2018}}
10. ^1 2 3 {{cite book|url=https://books.google.com/books?id=ip8_CwAAQBAJ&pg=PA574|title=Saunders Handbook of Veterinary Drugs: Small and Large Animal|last=Papich|first=Mark G.|publisher=Elsevier Health Sciences|year=2015|isbn=978-0-323-24485-5|page=574|ref=harv}}
11. ^1 2 3 4 5 {{cite book|url=https://books.google.com/books?id=YdREDwAAQBAJ&pg=PT2955|title=Veterinary Pharmacology and Therapeutics|last1=Riviere|first1=Jim E.|last2=Papich|first2=Mark G.|publisher=John Wiley & Sons|year=2017|isbn=978-1-118-85588-1|pages=2955-2966|ref=harv}}
12. ^1 2 {{cite journal|last1=Saridomichelakis|first1=Manolis N.|last2=Olivry|first2=Thierry|date=1 January 2016|title=An update on the treatment of canine atopic dermatitis|journal=The Veterinary Journal|volume=207|pages=29-37|doi=10.1016/j.tvjl.2015.09.016|issn=1090-0233|ref=harv}}
13. ^1 2 3 4 5 6 {{cite web|url=https://canna-pet.com/side-effects-apoquel-dogs/|title=Side Effects of Apoquel for Dogs|date=12 November 2017|work=Canna-Pet|accessdate=27 February 2018}}
14. ^1 2 3 {{cite web|url=https://vcahospitals.com/know-your-pet/oclacitinib|title=Oclacitinib|last=Barnette|first=Catherine|date=2017|work=VCA|publisher=LifeLearn|accessdate=27 February 2018}}
15. ^1 {{cite web|url=http://veterinarymedicine.dvm360.com/whats-new-with-old-problem-drug-options-treating-itch-canine-allergy?pageID=4|title=What's new with an old problem: Drug options for treating the itch of canine allergy|last1=Layne|first1=Elizabeth A.|last2=Moriello|first2=Karen A.|date=1 April 2015|work=dvm360|accessdate=27 February 2018}}
16. ^1 {{cite document|title=Apoquel, INN-oclacitinib maleate|accessdate=27 February 2018|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/veterinary/002688/WC500152091.pdf|publisher=European Medicines Agency}}
17. ^{{cite journal|last1=Cosgrove|first1=Sallie B.|last2=Wren|first2=Jody A.|last3=Cleaver|first3=Dawn M.|last4=Walsh|first4=Kelly F.|last5=Follis|first5=Stacey I.|last6=King|first6=Vickie I.|last7=Tena|first7=Jezaniah-Kira S.|last8=Stegemann|first8=Michael R.|date=1 December 2013|title=A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis|journal=Veterinary Dermatology|volume=24|issue=6|pages=587-e142|doi=10.1111/vde.12088|issn=1365-3164|ref=harv|pmc=4286885}}
18. ^1 2 {{cite journal|last1=Damsky|first1=William|last2=King|first2=Brett A.|date=1 April 2017|title=JAK inhibitors in dermatology: The promise of a new drug class|url=https://tpmgphysicianed.org/sites/tpmgphysicianed.org/files/JAKinhib2.pdf|journal=Journal of the American Academy of Dermatology|volume=76|issue=4|pages=736-744|doi=10.1016/j.jaad.2016.12.005|issn=0190-9622|ref=harv}}
19. ^{{cite journal|last1=Olivry|first1=Thierry|last2=Mayhew|first2=David|last3=Paps|first3=Judy S.|last4=Linder|first4=Keith E.|last5=Peredo|first5=Carlos|last6=Rajpal|first6=Deepak|last7=Hofland|first7=Hans|last8=Cote-Sierra|first8=Javier|date=1 October 2016|title=Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions|journal=Journal of Investigative Dermatology|volume=136|issue=10|pages=1961-1969|doi=10.1016/j.jid.2016.05.117|issn=0022-202X|ref=harv}}
20. ^1 {{cite journal|last1=Fukuyama|first1=Tomoki|last2=Ganchingco|first2=Joy Rachel|last3=Bäumer|first3=Wolfgang|date=5 January 2017|title=Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib|journal=European Journal of Pharmacology|volume=794|pages=20-26|doi=10.1016/j.ejphar.2016.11.020|issn=0014-2999|ref=harv}}
External links
- {{Official website|https://www.zoetisus.com/products/dogs/apoquel/index.aspx}}
{{Cytokine receptor modulators}} 4 : Non-receptor tyrosine kinase inhibitors|Pyrrolopyrimidines|Sulfonamides|Veterinary drugs
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