Desloratadine (trade names Clarinex and Aerius) is a tricyclic H₁ inverse agonist that is used to treat allergies. It is an

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

of loratadine. It was patented in 1984 and came into medical use in 2001.

Medical uses

Desloratadine is used to treat allergic rhinitis, nasal congestion and chronic idiopathic urticaria (

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

). It is the major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of loratadine and the two drugs are similar in safety and effectiveness. Desloratadine is available in many dosage forms and under many trade names worldwide. An emerging indication for desloratadine is in the treatment of acne, as an inexpensive adjuvant to isotretinoin and possibly as maintenance therapy or monotherapy.

Side effects

The most common side-effects are

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

(1.2%), dry mouth (3%), and

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

(0.6%).

Interactions

Co-administration with

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

, azithromycin,

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. The development of longer-acting H2 rec ...

resulted in elevated blood plasma concentrations of desloratadine and its

3-hydroxydesloratadine in studies. However, no clinically relevant changes were observed.

Pharmacology

Pharmacodynamics

Desloratadine is a selective H₁- antihistamine which functions as an

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

at the histamine H₁ receptor. At very high doses, is also an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses.

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 protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...

s. Desloratadine is metabolized to 3-hydroxydesloratadine in a three-step sequence in normal metabolizers. First, n-glucuronidation of desloratadine by

UGT2B10 UDP-glucuronosyltransferase 2B10 is an enzyme that in humans is encoded by the ''UGT2B10'' gene. It is responsible for glucuronidation of nicotine and cotinine. See also * UGT2B17 UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is ...

; then, 3-hydroxylation of desloratadine N-glucuronide by

CYP2C8 Cytochrome P4502C8 (abbreviated CYP2C8), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-cha ...

; and finally, a non-enzymatic deconjugation of 3-hydroxydesloratadine N-glucuronide. Both desloratadine and 3-hydroxydesloratadine are eliminated via urine and feces with a half-life of 27 hours in normal metabolizers.

Drugs.com Drugs.com is an online pharmaceutical encyclopedia that provides drug information for consumers and healthcare professionals, primarily in the United States. It self-describes its information as "accurate and independent" yet limited to being " ...

: Desloratadine . 3-Hydroxydesloratadine skeletal

It exhibits only peripheral activity since it does not readily cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...

; 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 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

system. It was found to weakly inhibit

CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Funct ...

, CYP2D6, and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

/ CYP3A5, and not to inhibit CYP1A2,

, CYP2C9, or CYP2C19. Desloratadine was found to be a potent and relatively selective inhibitor of

, a weak to moderate inhibitor of

UGT2B17 UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is encoded by the ''UGT2B17'' gene. UGT2B17 belongs to the family of UDP-glucuronosyltransferases (UGTs; EC 2.4.1.17), enzymes that catalyze the transfer of glucuronic acid from uridine ...

UGT1A10 UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the ''UGT1A10'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroid ...

, and UGT2B4, and not to inhibit UGT1A1, UGT1A3,

UGT1A4 UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the ''UGT1A4'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids ...

UGT1A6 UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the ''UGT1A6'' gene. Function UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic ...

, UGT1A9, UGT2B7,

UGT2B15 UDP-glucuronosyltransferase 2B15 is an enzyme that in humans is encoded by the ''UGT2B15'' gene. The UGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. UGT2B8 demo ...

UGT1A7 UDP glucuronosyltransferase 1 family, polypeptide A7 is a protein that in humans is encoded by the ''UGT1A7'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecu ...

, and

UGT1A8 UDP-glucuronosyltransferase 1-8 is an enzyme that in humans is encoded by the ''UGT1A8'' gene. Function This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such a ...

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.

References

External links

* {{Portal bar , Medicine Benzocycloheptapyridines Chloroarenes H1 receptor antagonists Human drug metabolites Peripherally selective drugs Piperidines Schering-Plough brands Merck & Co. brands