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]
Clinical data | |
---|---|
Trade names | Clarinex, Aerius, Allex, others[1][2] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a602002 |
License data | |
Pregnancy category |
|
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 | |
| |
CAS Number |
|
PubChem CID |
|
IUPHAR/BPS |
|
DrugBank |
|
ChemSpider |
|
UNII |
|
KEGG |
|
ChEBI |
|
ChEMBL |
|
CompTox Dashboard (EPA) |
|
ECHA InfoCard | 100.166.554 |
Chemical and physical data | |
Formula | C19H19ClN2 |
Molar mass | 310.83 g·mol−1 |
3D model (JSmol) |
|
| |
| |
(verify) |
It was patented in 1984 and came into medical use in 2001.[4]
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]
The most common side-effects are fatigue (1.2%[9]), dry mouth (3%[9]), and headache (0.6%[9]).[5]
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]
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]
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]
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]
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]
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.