Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE.

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Martinez-Gomez MA, Villanueva-Camanas RM, Sagrado S, Medina-Hernandez MJ

Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE.

Electrophoresis. 2007 Aug;28(15):2635-43. doi: 10.1002/elps.200600742.

PubMed ID

17605150 [ View in PubMed

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Abstract

The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with alpha(1)-acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants of drug enantiomers to HSA and the evaluation of the binding sites of antihistamines on the HSA molecule. The developed methodology includes the ultrafiltration of samples containing HSA and racemic antihistaminic drugs and the analysis of the free or bound drug fraction using the affinity EKC-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of antihistamines to HSA, the major plasmatic protein.

DrugBank Data that Cites this Article

Drugs

Hydroxyzine

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Hydroxyzine	Serum albumin	Protein	Humans	Unknown	Substrate Regulator	Details