Desloratadine

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Desloratadine
Desloratadine.svg
Desloratadine 3D ball-and-stick.png
Clinical data
Trade names Clarinex (US), Aerius, Dasselta, Deslordis (EU), others
AHFS/Drugs.com Monograph
MedlinePlus a602002
License data
Pregnancy
category
  • AU: B1
  • US: C (Risk not ruled out)
Routes of
administration
Oral (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
Elimination half-life 27 hours
Duration of action up to 24 hours
Excretion 40% as conjugated metabolites into urine
Similar amount into the feces
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.166.554 Edit this at Wikidata
Chemical and physical data
Formula C19H19ClN2
Molar mass 310.82 g/mol
3D model (JSmol)
  (verify)

Desloratadine (trade name Clarinex in the US and Aerius in Europe and Canada) is a tricyclic H1-antihistamine that is used to treat allergies. It is an active metabolite of loratadine.

Medical uses[edit]

Desloratadine is used to treat allergic rhinitis and nasal congestion.[1] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness.[1] Desloratadine is available in many dosage forms and under many trade names worldwide.[2]

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.[3][4]

Side effects[edit]

The most common side-effects are fatigue, dry mouth, and headache.[1]

Interactions[edit]

A number of drugs and other substances that are prone to interactions, such as ketoconazole, erythromycin and grapefruit juice, have shown no influence on desloratadine concentrations in the body. Desloratadine is judged to have a low potential for interactions.[5]

Pharmacology[edit]

Mechanism of action[edit]

Desloratadine is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor.[6]

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.[7]

Pharmacokinetics[edit]

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.[5]

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.[8] Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.[5][9]

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.[10]

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.[8]

3-Hydroxydesloratadine, the main metabolite

Pharmacogenomics[edit]

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.[5][9]

See also[edit]

References[edit]

  1. ^ a b c See S (2003). "Desloratadine for allergic rhinitis". Am Fam Physician. 68 (10): 2015–6. PMID 14655812.
  2. ^ Drugs.com Desloratadine entry at drugs.com international Page accessed May 4, 2015
  3. ^ Lee HE, Chang IK, Lee Y, Kim CD, Seo YJ, Lee JH, Im M (2014). "Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study". J Eur Acad Dermatol Venereol. 28 (12): 1654–60. doi:10.1111/jdv.12403. PMID 25081735.
  4. ^ Layton AM (2016). "Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris". Dermatol Clin. 34 (2): 147–57. doi:10.1016/j.det.2015.11.008. PMID 27015774.
  5. ^ a b c d "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. 2017-06-07.
  6. ^ Canonica GW, Blaiss M (2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". World Allergy Organ J. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457.
  7. ^ "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 2006-04-03.
  8. ^ a b Kazmi, F.; Yerino, P.; Barbara, J. E.; Parkinson, A. (2015-07-01). "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. American Society for Pharmacology & Experimental Therapeutics (ASPET). 43 (9): 1294–1302. doi:10.1124/dmd.115.065011. ISSN 1521-009X.
  9. ^ a b Drugs.com: Desloratadine Monograph.
  10. ^ Mann R, Pearce G, Dunn N, Shakir S (2000). "Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice". BMJ. 320 (7243): 1184–6. doi:10.1136/bmj.320.7243.1184. PMC 27362. PMID 10784544.