Desloratadine

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Desloratadine
Desloratadine.svg
Desloratadine 3D ball-and-stick.png
Clinical data
Trade namesClarinex (US), Aerius, Dasselta, Deslordis (EU), others
AHFS/Drugs.comMonograph
MedlinePlusa602002
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
BioavailabilityRapidly absorbed
Protein binding83 to 87%
MetabolismUGT2B10, CYP2C8
Metabolites3-Hydroxydesloratadine
Onset of actionwithin 1 hour
Elimination half-life27 hours
Duration of actionup to 24 hours
Excretion40% as conjugated metabolites into urine
Similar amount into the feces
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.166.554 Edit this at Wikidata
Chemical and physical data
FormulaC19H19ClN2
Molar mass310.82 g/mol g·mol−1
3D model (JSmol)
  (verify)

Desloratadine (trade name Clarinex and Aerius) is a tricyclic H1 antagonist that is used to treat allergies. It is an active metabolite of loratadine.

It was patented in 1984 and came into medical use in 2001.[1]

Medical uses[edit]

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (hives).[2] It is the major metabolite of loratadine and the two drugs are similar in safety and effectiveness.[2] Desloratadine is available in many dosage forms and under many trade names worldwide.[3]

An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.[4][5]

Side effects[edit]

The most common side-effects are fatigue, dry mouth, and headache.[2]

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.[6]

Pharmacology[edit]

Pharmacodynamics[edit]

Desloratadine is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor.[7]

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.[8]

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.[6]

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.[9] Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.[6][10]

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.[11]

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.[9]

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.[6][10]

See also[edit]

References[edit]

  1. ^ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 549. ISBN 9783527607495.
  2. ^ a b c See S (2003). "Desloratadine for allergic rhinitis". Am Fam Physician. 68 (10): 2015–6. PMID 14655812.
  3. ^ Drugs.com Desloratadine entry at drugs.com international Page accessed May 4, 2015
  4. ^ 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.
  5. ^ 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.
  6. ^ a b c d "Aerius: EPAR – Product Information" (PDF). European Medicines Agency. 2017-06-07.
  7. ^ 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.
  8. ^ "Aerius: EPAR – Scientific Discussion" (PDF). European Medicines Agency. 2006-04-03.
  9. ^ 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. 43 (9): 1294–1302. doi:10.1124/dmd.115.065011. ISSN 1521-009X. PMID 26135009.
  10. ^ a b Drugs.com: Desloratadine Monograph.
  11. ^ 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.