Molecular properties and pharmacokinetic behavior of cetirizine, a zwitterionic H1-receptor antagonist

Journal of Medicinal Chemistry
Alessandra PagliaraJ P Rihoux

Abstract

The ionization and lipophilicity behavior of the antihistamine (H1-receptor antagonist) cetirizine was investigated, showing the drug to exist almost exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its octanol/water lipophilicity is constant and low compared to cationic antihistamines (log D = log PZ = 1.5), whereas its H-bonding capacity is relatively large (delta log PZ > or = 3.1). Conformational, electronic, and lipophilicity potential calculations revealed that zwitterionic cetirizine experiences partial intramolecular charge neutralization in folded conformers of lower polarity. Pharmacokinetic investigations have shown the drug to be highly bound to blood proteins, mainly serum albumin, and to have a low brain uptake, explaining its lack of sedative effects. As such, cetirizine does not differ from "second-generation" antihistamines. In contrast, its very low apparent volume of distribution in humans (0.4 L kg-1, smaller than that of exchangeable water) implies a low affinity for lean tissues such as the myocardium and is compatible with the absence of cardiotoxicity of the drug. The zwitterionic nature and modest lipophilicity of cetirizine may account for this pharmacokinetic behavior. The sugge...Continue Reading

References

Dec 1, 1990·The Journal of Allergy and Clinical Immunology·A M Snowman, S H Snyder
Jan 1, 1985·European Journal of Clinical Pharmacology·A F CohenA W Peck
Aug 1, 1988·Biochemical Pharmacology·S UrienJ P Tillement
Jul 1, 1985·British Journal of Clinical Pharmacology·O Brørs, S Jacobsen
Apr 1, 1994·Journal of Computer-aided Molecular Design·P GaillardA Boudon
Mar 1, 1996·Pharmaceutical Research·B TestaP Weber
Feb 20, 2002·Chemical Reviews·Alessandra PagliaraBernard Testa
Sep 1, 1955·The Journal of Clinical Investigation·R J HAVELJ H BRAGDON

❮ Previous
Next ❯

Citations

Jun 3, 2000·Archives of Pharmacal Research·S O ChoiH Y Choo
Sep 14, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·S O ChoiH Y Choo
Dec 3, 1999·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·J P Rihoux
Aug 11, 1999·Pharmaceutical Science & Technology Today·G CaronB Testa
May 7, 2013·Journal of Chemical Information and Modeling·Senthil NatesanStefan Balaz
Apr 11, 2003·Fundamental & Clinical Pharmacology·Françoise BreeJean-Paul Tillement
Jul 15, 2005·Skin Pharmacology and Physiology·Malcolm W Greaves
Mar 29, 2001·Drugs·G M WalshH Timmerman
Dec 22, 2006·Drugs·Jeffrey M Lehman, Michael S Blaiss
Dec 14, 1999·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·S Hayashi, S Hashimoto
May 7, 2002·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·K Y Tam, L Quéré
Dec 22, 2011·Drug Development and Industrial Pharmacy·Mladen Stojanov, Kim L Larsen
Mar 21, 2007·Expert Opinion on Investigational Drugs·Costas GiaginisAnna Tsantili-Kakoulidou
Jun 22, 2007·The Veterinary Journal·Lena OlsénCarina Ingvast-Larsson
Aug 18, 2004·Fundamental & Clinical Pharmacology·M MolimardM Strolin Benedetti
Sep 6, 2003·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·S T HolgateUNKNOWN Consensus Group on New-Generation Antihistamines
May 3, 2007·Journal of Veterinary Pharmacology and Therapeutics·L OlsénP Larsson
Sep 12, 2006·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·M PasqualiG W Canonica
Jan 6, 2006·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P Devillier
Nov 18, 2005·Bioorganic & Medicinal Chemistry Letters·Donald S MiddletonMichael Trevethick
Jun 17, 2008·Journal of Pharmaceutical Sciences·Costas Giaginis, Anna Tsantili-Kakoulidou
Mar 3, 2004·Medicinal Research Reviews·Georgette Plemper van BalenBernard Testa
Jun 23, 2006·Biopharmaceutics & Drug Disposition·Anubha GuptaE Niclas Jonsson
Jun 21, 2006·Electrophoresis·Ann Van Eeckhaut, Yvette Michotte
Feb 27, 2008·Journal of Separation Science·Yu-Wei ChouSu-Hwei Chen
Nov 26, 2009·Chemistry & Biodiversity·Gabriele CrucianiLaura Goracci
Jun 23, 2001·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·M Malik, A J Camm
Mar 10, 2001·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·A P Ten EickM D Reed
May 21, 2020·ChemMedChem·Károly Mazák, Béla Noszál
Feb 19, 2011·The Analyst·Arnold BahlmannRudolf J Schneider
Sep 7, 2018·BioMed Research International·Alaa N A FahmiHatem A Salem
Apr 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Babiker M El-Haj, Samrein B M Ahmed
Jul 22, 2014·Environmental Toxicology and Chemistry·Ralph N MeadRobert J Kieber
Dec 13, 2019·Multidisciplinary Respiratory Medicine·Angelo G CorsicoGiorgio Ciprandi
Jun 24, 2020·Journal of Computer-aided Molecular Design·Almudena PeronaFederico Gago

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.