Cetirizine

Cetirizine

Systematic (IUPAC) name
(±)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1- piperazinyl]ethoxy]acetic acid
Clinical data
Trade names	Zyrtec
AHFS/Drugs.com	monograph
MedlinePlus	a698026
Licence data	US FDA:link
Pregnancy cat.	B(US)
Legal status	GSL (UK) OTC (US) OTC in Canada
Routes	Oral
Pharmacokinetic data
Bioavailability	well absorbed
Protein binding	~93%
Metabolism	Excreted mainly unchanged
Half-life	8.3 Hours
Excretion	Urine (mainly), hepatic or excrement (Small amounts)
Identifiers
CAS number	83881-51-0
ATC code	R06AE07
PubChem	CID 2678
IUPHAR ligand	1222
DrugBank	APRD00630
ChemSpider	2577 Y
UNII	YO7261ME24 Y
KEGG	D07662 Y
ChEBI	CHEBI:3561 Y
ChEMBL	CHEMBL1000 Y
Synonyms	Alatrol, Alzene, Cetirizina, Cetirin, Cetzine, Cetirizin, Cezin, Humex, Letizen, Razene, Reactine, Zyrtec, Zirtec, Zodac, Zirtek, Zynor, Zyrlek, Zyllergy
Chemical data
Formula	C21H25ClN2O3
Mol. mass	388.89
SMILES	eMolecules & PubChem
InChI InChI=1S/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26) Y Key:ZKLPARSLTMPFCP-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Cetirizine ( /sɛˈtɪrɨziːn/), a second-generation antihistamine, is a major metabolite of hydroxyzine, and a racemic selective H₁ receptor inverse agonist used in the treatment of allergies, hay fever, angioedema, and urticaria.

Availability

Formerly prescription-only in the USA and Canada, cetirizine is now available over-the-counter in both countries as Zyrtec and Reactine respectively. Zyrtec was the highest-grossing new non-food product of 2008 in the US, generating sales of $315.9 million.^[1] It is also available as a generic drug. In Australia, Zyrtec is available over-the-counter in pharmacies and in the UK cetirizine can be sold in limited quantities off-the-shelf in any outlet and is often available in supermarkets. As of 2009, Germany made many generic drugs containing cetirizine available in pharmacies without prescription.^[2] Norway, Sweden^[3] and Finland also recognize Cetirizine as an over-the-counter medicine. In India it is sold over-the-counter as brand-name 'Cetzine', even though it remains classified as a Schedule H (prescription) drug^[4]

Pharmacology

Cetirizine crosses the blood-brain barrier only slightly, reducing the sedative side-effect common with older antihistamines. ^[5] It has also been shown to inhibit eosinophil chemotaxis and LTB4 release. At a dosage of 20 mg, Boone et al. found that it inhibited the expression of VCAM-1 in patients with atopic dermatitis.^[6]

The levorotary enantiomer of cetirizine, known as levocetirizine, is the more active form.

L-Stereosimer, levocetirizine (top) and D-stereoisomer of cetirizine

Administration method and metabolism

Chewable, non-chewable, and syrup forms of cetirizine are similarly absorbed rapidly and effectively, with absorbed food minutely affecting the absorption rate which yields a peak serum level one hour after administration;^[7] in a study of healthy volunteers prescribed 10 mg tablets, once daily for 10 days, a mean peak serum level of 311 ng/mL was observed.^[8] The metabolic effects of cetirizine are long acting, remaining in the system for a maximum of 21 hours before being excreted; the average elimination half-life is 8 hours. About 70% of the drug is removed through urination, of which half is observed as unchanged cetirizine compound. Another 10% is excreted.^[7][8]

Like many other antihistamine medications, cetirizine is commonly prescribed in combination with pseudoephedrine hydrochloride, a decongestant. These combinations are marketed using the same brand name as the cetirizine with a "-D" suffix (Zyrtec-D, Virlix-D, etc.)

Formerly only available by a prescription, both Zyrtec and Zyrtec-D in November 2007 became available over-the-counter in the United States.^[9]

Indications

Allergies

Cetirizine's primary indication is for hay fever and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H1 receptor, blocking those receptors temporarily relieves those symptoms.

Rhinovirus infection

Interleukin 6 and interleukin 8 have been shown to be elevated in acute respiratory distress syndrome.^[10] Cetirizine contains L- and D-stereoisomers. Chemically, levocetirizine is the active L-enantiomer of cetirizine. In a recent study of airway epithelial cells the following was observed: Levocetirizine inhibits the production of intercellular adhesion molecule ICAM-1 and secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiologic changes related to human rhinovirus (HRV) infection. Levocetirizine treatment inhibited the HRV-induced increase in ICAM-1 mRNA and protein levels, as well as the HRV-induced expression of IL-6 and IL-8 mRNA and protein levels. Viral titer, as measured by culture in MRC-5 cells, was reduced by levocetirizine. Levocetirizine treatment also reduced the increased nuclear factor-kappa B (NF-κB) expression seen with HRV infection. Levocetirizine inhibited the expression of Toll-like receptor 3 (TLR3) mRNA and protein levels. These findings indicate that, in HNEC and A549 cells, levocetirizine inhibits HRV replication and HRV-induced upregulation of ICAM-1, IL-6, and IL-8, TLR3 expression and NF-κB activation. The results of this study suggest that levocetirizine may have a possible clinical application in the treatment of airway inflammation caused by HRV infection.^[11] Airway inflammation caused from a cytokine storm secondary to acute respiratory distress syndrome could also theoretically benefit.

Kimura's disease

Cetirizine is an effective agent in treating the symptoms of Kimura's disease, which mostly occurs in young Asian men, affecting the lymph nodes and soft tissue of the head and neck in the form of tumor-like lesions. Cetirizine's properties of being effective both in the treatment of pruritus (itching) and as an anti-inflammatory agent make it suitable for the treatment of the pruritus associated with these lesions.^[12] In a 2005 study, the American College of Rheumatology conducted treatments initially using prednisone, followed by steroid dosages and azathioprine, omeprazole, and calcium and vitamin D supplements over the course of two years.^[12] The skin condition of the patient began to improve and the skin lesions lessened. However, there were symptoms of cushingoid and hirsutism observed before the patient was removed from the courses of steroids and placed on 10 mg/day of cetirizine to prevent skin lesions;^[12] an agent suitable for the treatment of pruritus associated with such lesions.^[12] Asymptomatically, the patient's skin lesions disappeared after treatment with cetirizine, blood eosinophil counts became normal,^[12] corticosteroid effects were resolved,^[12] and a remission began within a period of two months.^[12] It is also thought that the inhibition of eosinophils may be the key to treatment of Kimura's disease due to the role of eosinophils, rather than other cells with regards to the lesions of the skin.^[12]

Side Effects

Dryness of the mouth, nose and throat, urinary retention, blurred vision and stomach ache are commonly reported side effects of this drug.^[13]

Synthesis

The following synthesis of this compound was reported in 1985:^[14]

References

1. ^ Elliott, Stuart (24 March 2009). "A Strategy When Times Are Tough: "It's New!"". The New York Times. http://www.nytimes.com/2009/03/25/business/media/25adco.html. Retrieved 26 March 2009. 
2. ^ "Cetirizin". http://de.wikipedia.org/wiki/Cetirizin. 
3. ^ "Cetirizin". http://receptfria.se/sandoz_camp/front/front/visa_underkategori?h_kategori_id=5&u_kategori_id=12. 
4. ^ Drugs and Cosmetics (2nd amendment) rules, 2006. item 104 in schedule H.
5. ^ Gupta, A; Chatelain P, Massingham R, Jonsson EN, Hammarlund-Udenaes M (February 2006). [dmd.aspetjournals.org/content/34/2/318.long "Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)"]. Drug Metab. Dispos. 34 (2): 318–23. doi:10.1124/dmd.105.007211. PMID 16303872. dmd.aspetjournals.org/content/34/2/318.long. 
6. ^ Boone M, Lespagnard L, Renard N, Song M, Rihoux JP (July 2000). "Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine". J Eur Acad Dermatol Venereol 14 (4): 263–6. doi:10.1046/j.1468-3083.2000.00017.x. PMID 11204513. http://www3.interscience.wiley.com/journal/119045164/abstract?CRETRY=1&SRETRY=0. Retrieved 2009-11-19. 
7. ^ ^{a b} Anderson, Philip; Knoben, James E.; Troutman, William G. (2002). Handbook of clinical drug data. New York: McGraw-Hill. p. 807. ISBN 0-07-136362-9. 
8. ^ ^{a b} "Zyrtec prescribing information". May 2006. http://www.pfizer.com/files/products/uspi_zyrtec.pdf. Retrieved 2009-11-19. 
9. ^ Payne, January W (2008-01-09). "Over-the-Counter Zyrtec: a Money-Saver?". U.S. News & World Report. http://health.usnews.com/articles/health/2008/01/09/over-the-counter-zyrtec-is-about-to-arrive.html. 
10. ^ Chollet-Martin, S; Montravers, P; Gibert, C; Elbim, C; Desmonts, JM; Fagon, JY; Gougerot-Pocidalo, MA (1993). "High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome.". Infection and immunity 61 (11): 4553–9. PMC 281204. PMID 8406851. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=281204. 
11. ^ Jang YJ, Wang JH, Kim JS, Kwon HJ, Yeo NK, Lee BJ (March 2009). "Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells". Antiviral Res. 81 (3): 226–33. doi:10.1016/j.antiviral.2008.12.001. PMID 19110001. 
12. ^ ^{a b c d e f g h} Ben-Chetrit E, Amir G, Shalit M (February 2005). "Cetirizine: An effective agent in Kimura's disease". Arthritis Rheum. 53 (1): 117–8. doi:10.1002/art.20908. PMID 15696573. 
13. ^ British National Formulary (BNF) 61. 2011. 
14. ^ Baltes, E.; De Lannoy, J.; Rodriguez, L.; 1985, U.S. Patent 4,525,358.

Books and journals

1. Anderson, P. O., Knoben, J. E., et al. (2002) Handbook of clinical drug data 10th ed. McGraw-Hill International
2. Pfizer Inc, et al. (2006) ZYRTEC (cetirizine hydrochloride) Tablets, Chewable Tablets and Syrup For Oral Use Pfizer Incorporated publications
3. Chetrit, E. B., Amir, G., Shalit, M. (2005). Cetirizine: an effective agent in Kimura's Disease Arthritis & Rheumatism (Arthritis care & research) Vol 53, p117-118

External links

• Zyrtec prescribing information Pfizer
• List of brand names
• US FDA approves Zyrtec-D for over the counter sales
• US FDA approves Zyrtec for over the counter sales
• U.S. National Library of Medicine: Drug Information Portal - Cetirizine