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Desloratadine (trade name Clarinex in the US and Aerius in Europe and Canada) is a tricyclic H 1 -antihistamine that is used to treat allergies. It is an active metabolite of loratadine.
1 Medical uses
2 Side effects
4.1 Mechanism of action
5 See also
Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria ( hives ).
An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.
The most common side-effects are fatigue, dry mouth, and headache.
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.
Mechanism of action
Desloratadine is a selective H 1 – antihistamine which functions as an inverse agonist at the histamine H 1 receptor.
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.
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.
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.
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.
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.
3-Hydroxydesloratadine, the main metabolite
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.
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