Desloratadine

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Desloratadine
Desloratadine.svg
Desloratadine 3D ball-and-stick.png
Clinical data
Trade names Clarinex, Aerius, Allex, others [1] [2]
AHFS/Drugs.com Monograph
MedlinePlus a602002
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		By mouth (tablets, solution)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Rapidly absorbed
Protein binding 83 to 87%
Metabolism UGT2B10, CYP2C8
Metabolites 3-Hydroxydesloratadine
Onset of action within 1 hour [3]
Elimination half-life 27 hours [3]
Duration of action up to 24 hours [3]
Excretion 40% as conjugated metabolites into urine
Similar amount into the feces
Identifiers
  • 8-chloro-6,11-dihydro-11-(4-piperdinylidene)- 5H-benzo[5,6]cyclohepta[1,2-b]pyridine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.166.554 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H19ClN2
Molar mass 310.83 g·mol−1
3D model (JSmol)
  • Clc4cc2c(C(/c1ncccc1CC2)=C3/CCNCC3)cc4
  • InChI=1S/C19H19ClN2/c20-16-5-6-17-15(12-16)4-3-14-2-1-9-22-19(14)18(17)13-7-10-21-11-8-13/h1-2,5-6,9,12,21H,3-4,7-8,10-11H2 Yes check.svgY
  • Key:JAUOIFJMECXRGI-UHFFFAOYSA-N Yes check.svgY
   (verify)

Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine. [3]

Contents

It was patented in 1984 and came into medical use in 2001. [4]

Medical uses

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives). [5] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness. [5] Desloratadine is available in many dosage forms and under many trade names worldwide. [6]

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy. [7] [8]

Side effects

The most common side-effects are fatigue (1.2% [9] ), dry mouth (3% [9] ), and headache (0.6% [9] ). [5]

Interactions

Co-administration with erythromycin, ketoconazole, azithromycin, fluoxetine or cimetidine resulted in elevated blood plasma concentrations of desloratadine and its metabolite 3-hydroxydesloratadine in studies. However, no clinically relevant changes were observed. [10] [11]

Pharmacology

Pharmacodynamics

Desloratadine is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor. [12]

At very high doses, is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses. [13]

Pharmacokinetics

Desloratadine is well absorbed from the gut and reaches highest blood plasma concentrations after about three hours. In the bloodstream, 83 to 87% of the substance are bound to plasma proteins. [11]

Desloratadine is metabolized to 3-hydroxydesloratadine in a three-step sequence in normal metabolizers. First, n-glucuronidation of desloratadine by UGT2B10; then, 3-hydroxylation of desloratadine N-glucuronide by CYP2C8; and finally, a non-enzymatic deconjugation of 3-hydroxydesloratadine N-glucuronide. [14] Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers. [11] [15]

3-Hydroxydesloratadine is the main metabolite. 3-Hydroxydesloratadine skeletal.svg
3-Hydroxydesloratadine is the main metabolite.

It exhibits only peripheral activity since it does not readily cross the blood–brain barrier; hence, it does not normally cause drowsiness because it does not readily enter the central nervous system. [16]

Desloratadine does not have a strong effect on a number of tested enzymes in the cytochrome P450 system. It was found to weakly inhibit CYP2B6, CYP2D6, and CYP3A4/CYP3A5, and not to inhibit CYP1A2, CYP2C8, CYP2C9, or CYP2C19. Desloratadine was found to be a potent and relatively selective inhibitor of UGT2B10, a weak to moderate inhibitor of UGT2B17, UGT1A10, and UGT2B4, and not to inhibit UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, UGT2B15, UGT1A7, and UGT1A8. [14]

Pharmacogenomics

2% of Caucasian people and 18% of people from African descent are desloratadine poor metabolizers. In these people, the drug reaches threefold highest plasma concentrations six to seven hours after intake, and has a half-life of about 89 hours. However, the safety profile for these subjects is not worse than for extensive (normal) metabolizers. [11] [15]

See also

Related Research Articles

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<span class="mw-page-title-main">Loratadine</span> Antihistamine medication

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References

  1. ↑ Murdoch D, Goa KL, Keam SJ (April 7, 2003). "Desloratadine: an update of its efficacy in the management of allergic disorders". Drugs. 63 (19): 2051–2077. doi:10.2165/00003495-200363190-00010. PMID   12962522. S2CID   195689362.
  2. ↑ "Allex EPAR". European Medicines Agency (EMA).
  3. 1 2 3 4 Lieberman P, Hernandez-Trujillo V, Lieberman J, Frew AJ (2008). "Antihistamines". Clinical Immunology. Elsevier. pp. 1317–1329. doi:10.1016/b978-0-323-04404-2.10089-2. ISBN   9780323044042. Desloratadine is a metabolite of loratadine. The onset of action is within 1 hour. Peak serum concentrations of desloratadine appear 3 hours after dosing. The mean elimination half-life of desloratadine is 27 hours and that of its metabolite is 36 hours. The consumption of food does not interfere with the absorption of desloratadine. Wheal inhibition is detected 1 hour after administration and may last 24 hours.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN   9783527607495.
  5. 1 2 3 See S (November 2003). "Desloratadine for allergic rhinitis". American Family Physician. 68 (10): 2015–2016. PMID   14655812. Archived from the original on 2005-07-24. Retrieved 2005-08-01.
  6. ↑ Drugs.com Desloratadine entry at drugs.com international Page accessed May 4, 2015
  7. ↑ Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, Im M (December 2014). "Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study". Journal of the European Academy of Dermatology and Venereology. 28 (12): 1654–1660. doi:10.1111/jdv.12403. PMID   25081735. S2CID   3406128.
  8. ↑ Layton AM (April 2016). "Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris". Dermatologic Clinics. 34 (2): 147–157. doi:10.1016/j.det.2015.11.008. PMID   27015774.
  9. 1 2 3 González-Núñez V, Valero A, Mullol J (May 2013). "Safety evaluation of desloratadine in allergic rhinitis". Expert Opinion on Drug Safety. Informa Healthcare. 12 (3): 445–453. doi:10.1517/14740338.2013.788148. PMID   23574541. S2CID   40472187.
  10. ↑ "Clarinex: Prescribing Information" (PDF). U.S. Food and Drug Administration . Retrieved 2022-01-21.
  11. 1 2 3 4 "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. Archived from the original (PDF) on 2019-07-05. Retrieved 2022-01-21.
  12. ↑ Canonica GW, Blaiss M (February 2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC   3500039 . PMID   23268457.
  13. ↑ "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 2006-04-03. Archived from the original (PDF) on 2018-03-16. Retrieved 2017-10-13.
  14. 1 2 Kazmi F, Yerino P, Barbara JE, Parkinson A (September 2015). "Further Characterization of the Metabolism of Desloratadine and Its Cytochrome P450 and UDP-glucuronosyltransferase Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor". Drug Metabolism and Disposition. 43 (9): 1294–1302. doi: 10.1124/dmd.115.065011 . PMID   26135009.
  15. 1 2 Drugs.com: Desloratadine Monograph .
  16. ↑ Mann RD, Pearce GL, Dunn N, Shakir S (April 2000). "Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice". BMJ. 320 (7243): 1184–1186. doi:10.1136/bmj.320.7243.1184. PMC   27362 . PMID   10784544.
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