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 dermat ...
. 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
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 breathin ...
and chronic idiopathic urticaria (
hives).
It is the major
metabolite of
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 ...
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 skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...
, 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 t ...
and possibly as maintenance therapy or monotherapy.
Side effects
The most common side-effects are fatigue (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 (0.6%).[
]
Interactions
Co-administration with erythromycin, 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, pneumo ...
, 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.
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 provid ...
which functions as an inverse agonist at the histamine H1 receptor.
At very high doses, is also an antagonist 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-rec ...
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 intr ...
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 at ...
of 27 hours in normal metabolizers.[ Drugs.com: Desloratadine .]
It exhibits only peripheral activity since it does not readily cross the blood–brain barrier; 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 p ...
.
Desloratadine does not have a strong effect on a number of tested enzymes in the cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...
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/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
...
, 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 ...
, 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 pat ...
, 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, UGT1A6, 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.
See also
* Benzocycloheptenes
* Azatadine
References
External links
*
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