Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
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Martinez-Gomez MA, Carril-Aviles MM, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
J Chromatogr A. 2007 Apr 20;1147(2):261-9. doi: 10.1016/j.chroma.2007.02.054. Epub 2007 Feb 22.
- PubMed ID
- 17339039 [ View in PubMed]
- Abstract
An important topic in the drug discovery and development process is the role of drug binding to plasma proteins. In this paper the characterization of the interaction between antihistamines (cationic drugs) towards human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) under physiological conditions by capillary electrophoresis-frontal analysis is presented. Furthermore, the binding of these drugs to all plasma proteins is evaluated by using ultrafiltration and capillary electrophoresis. Antihistamines present a wide-ranging behaviour with respect to their affinities towards plasma proteins. Orphenadrine, phenindamine, tripelenamine and tripolidine principally bind to HSA; carbinoxamine, dimetindene and etintidine principally bind to AGP; brompheniramine, chlorpheniramine and ranitidine present an important binding to lipoproteins and/or globulins and finally, chlorcyclizine, cinarizine, cyclizine, doxylamine, hydroxyzine, perphenazine and terfenadine do not bind to lipoproteins and/or globulins but bind to HSA and AGP in different extension. The interaction of antihistamines with HSA is determined by the hydrophobicity (direct relationship) and the polar surface area (indirect relationship) of the compounds. The steric parameters and hydrogen bonding character of compounds seems to be related with the binding of antihistamines to AGP. The antihistamine-HSA affinity constants were evaluated and the K(1) values ranged from 7 x 10(2)M(-1) (for doxylamine) to 4 x 10(4)M(-1) (for phenindamine).
DrugBank Data that Cites this Article
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Carbinoxamine alpha1-acid glycoprotein (Protein Group) Protein group Humans UnknownBinderRegulatorDetails Chlorcyclizine Serum albumin Protein Humans UnknownRegulatorDetails Cinnarizine Serum albumin Protein Humans UnknownRegulatorDetails Cyclizine Serum albumin Protein Humans UnknownRegulatorDetails Doxylamine Serum albumin Protein Humans UnknownRegulatorDetails Hydroxyzine Serum albumin Protein Humans UnknownSubstrateRegulatorDetails Orphenadrine Serum albumin Protein Humans UnknownBinderRegulatorDetails Perphenazine Serum albumin Protein Humans UnknownRegulatorDetails Phenindamine Serum albumin Protein Humans UnknownBinderRegulatorDetails Terfenadine alpha1-acid glycoprotein (Protein Group) Protein group Humans UnknownBinderRegulatorDetails Terfenadine Serum albumin Protein Humans UnknownBinderRegulatorDetails Tripelennamine Serum albumin Protein Humans UnknownBinderRegulatorDetails Triprolidine Serum albumin Protein Humans UnknownBinderRegulatorDetails