LEVOCETIRIZINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25ClN2O3.ClH
Molecular Weight	425.349
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of LEVOCETIRIZINE HYDROCHLORIDE

SMILES

Cl.OC(=O)COCCN1CCN(CC1)[C@H](C2=CC=CC=C2)C3=CC=C(Cl)C=C3

InChI

InChIKey=CUSPGNDCPOVPBA-ZMBIFBSDSA-N

InChI=1S/C21H25ClN2O3.ClH/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);1H/t21-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C21H25ClN2O3
Molecular Weight	388.888
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Levocetirizine dihydrochloride is the R enantiomer of cetirizine hydrochloride, a racemic compound with antihistaminic properties. Levocetirizine is a third-generation non-sedative antihistamine indicated for the relief of symptoms associated with seasonal and perennial allergic rhinitis and uncomplicated skin manifestations of chronic idiopathic urticaria. It was developed from the second-generation antihistamine cetirizine. Levocetirizine was approved by the United States Food and Drug Administration on May 25, 2007 and is marketed under the brand XYZAL. Its principal effects are mediated via selective inhibition of H1 receptors. The antihistaminic activity of levocetirizine has been documented in a variety of animal and human models. In vitro binding studies revealed that levocetirizine has an affinity for the human H1-receptor 2-fold higher than that of cetirizine (Ki = 3 nmol/L vs. 6 nmol/L, respectively). The clinical relevance of this finding is unknown.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 316	Antagonist 2,849		3.0 nM [Ki]
Histamine H1 receptor 316	Inverse Agonist 85		6.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Seasonal allergic rhinitis 64	Palliative	Approved 8,583	XYZAL
Perennial allergic rhinitis 47	Palliative	Approved 8,583	XYZAL
Chronic idiopathic urticaria 11	Palliative	Approved 8,583	XYZAL
Allergic rhinitis 104	Primary	Approved 8,583	XYZAL
Chronic Idiopathic Urticaria 3	Primary	Approved 8,583	XYZAL
Dermatitis 10	Primary	Phase III 665	XYZAL

C_max

Value	Dose	Analyte	Population
512.25 ng/mL	10 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
0.27 μg/mL	5 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
0.17 μg/mL	5 mg single, oral	LEVOCETIRIZINE blood	Homo sapiens

AUC

Value	Dose	Analyte	Population
4136.4 ng × h/mL	10 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
2.31 μg × h/mL	5 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
0.97 μg × h/mL	5 mg single, oral	LEVOCETIRIZINE blood	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
7.76 h	10 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
7.05 h	5 mg single, oral	LEVOCETIRIZINE plasma	Homo sapiens
6.83 h	5 mg single, oral	LEVOCETIRIZINE blood	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
4.5%	5 mg single, oral		LEVOCETIRIZINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
20 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 18–60 years
5 mg 1 times / day steady, oral Recommended	unhealthy, 48-64 years	Disc. AE: Hepatotoxicity...
5 mg 1 times / day steady, oral Recommended	unhealthy, > 12 years	Disc. AE: Somnolence, Fatigue...

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AEs

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AE	Significance	Dose	Population
Hepatotoxicity	2 patients Disc. AE	5 mg 1 times / day steady, oral Recommended	unhealthy, 48-64 years
Asthenia	2.3% Disc. AE	5 mg 1 times / day steady, oral Recommended	unhealthy, > 12 years
Fatigue	2.3% Disc. AE	5 mg 1 times / day steady, oral Recommended	unhealthy, > 12 years
Somnolence	2.3% Disc. AE	5 mg 1 times / day steady, oral Recommended	unhealthy, > 12 years

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252 inducer 1,087	inhibitor 2,438 inducer 440	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2C19 2,057 CYP2E1 1,060 P-gp 1,741	P-gp 2,052 OATP1A2 67 OAT4 93 OATP1B1 503 OATP1B3 435	CYP1A2 832 UGT1A1 78

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 2,333	inducer 1,966	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2C19 2,141	inhibitor 4,027	no
CYP2C9 2,497	inducer 1,966	no
CYP2C9 2,497	inhibitor 4,027	no

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Drug as victim

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Target	Modality	Activity
OAT4 93	substrate 4,014	likely
OATP1A2 67	substrate 4,014	likely
CYP2D6 1,388	substrate 4,014	no
OATP1B1 503	substrate 4,014	no
OATP1B3 435	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-6286	http://www.3bsc.com/index/pro_info.php?id=115439
Alfa Chemistry	130018-77-8	https://www.alfa-chemistry.com/levocetirizine-cas-130018-77-8-item-289953.htm
Alichem	139002959	http://www.alichem.com/en/products/130018-77-8.html
AvaChem Scientific	1666B	http://www.avachem.com/productSearch.asp?1666B
BenchChem	B532939	https://www.benchchem.com/product/b532939

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PubMed

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Title	Date	PubMed
The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare.	2001	11922397
Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers.	2001 Aug	11564134
A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers.	2001 Jan	11167352
The new antihistamines--desloratadine and levocetirizine: a review.	2002 Dec	12851991
A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects.	2002 Feb	11868924

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Patents

Sample Use Guides

In Vivo Use Guide

Allergic Rhinitis: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients. Chronic Idiopathic Urticaria: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.

Route of Administration: Oral

In Vitro Use Guide

Equilibrium binding experiments on CHO cells expressing H1 receptor were performed using [3H]mepyramine as a radiolabel ligand.

Substance Class	Chemical
Record UNII	W69HSF2416
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOCETIRIZINE HYDROCHLORIDE

Common Name

English

ACETIC ACID, 2-(2-(4-((R)-(4-CHLOROPHENYL)PHENYLMETHYL)-1-PIPERAZINYL)ETHOXY)-, HYDROCHLORIDE (1:1)

Preferred Name

English

LEVOCETIRIZINE MONOHYDROCHLORIDE

Common Name

English

CETIRIZINE HYDROCHLORIDE (R)-

Common Name

English

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Code System

Code

Type

Description

CAS

823178-28-5

PRIMARY

EVMPD

SUB25911

PRIMARY

FDA UNII

W69HSF2416

PRIMARY

PUBCHEM

67336450

PRIMARY

EVMPD

SUB25904

PRIMARY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator