Desloratadine (trade names Clarinex and Aerius) is a

tricyclic Tricyclics are chemical compounds that contain three interconnected rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. Among these are antid ...

H₁ inverse agonist that is used to treat

allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

. 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 ...

loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in combination with pseudoephedrine, a decongestant, known as lora ...

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

Medical uses

Desloratadine is used to treat

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathing. ...

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 ...

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 Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

, as an inexpensive adjuvant to

isotretinoin Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers (squamous-cell carcinoma), and in th ...

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 Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

(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,

azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...

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 Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

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 receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

s. 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 Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...

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; 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 Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of 27 hours in normal metabolizers. Drugs.com: 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 Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

because it does not readily enter the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

. 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 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

, 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 Cytochrome P450 3A5 is a protein that in humans is encoded by the ''CYP3A5'' gene. Tissue distribution ''CYP3A5'' encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the cytochrome P450, the CYP3A5 is expressed in the ...

, and not to inhibit

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

, or

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...

. Desloratadine was found to be a potent and relatively selective inhibitor of UGT2B10, a weak to moderate inhibitor of UGT2B17, UGT1A10, and

UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the ''UGT2B4'' gene. Function UGT2B4 is mainly involved in the glucuronidation of hyodeoxycholic acid, a bile acid, and cate ...

, and not to inhibit

UGT1A1 UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT), an enzyme of the glucuronidation path ...

UGT1A3 UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the ''UGT1A3'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, ...

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 UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the ''UGT1A9'' gene. Function This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such a ...

UGT2B7 UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltrans ...

, UGT2B15,

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.

Pharmacogenomics

2% of Caucasian people and 18% of people from African descent are desloratadine

poor metabolizer Pharmacogenomics is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup of an individual affects the ...

s. 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