Characterization of basic drug-human serum protein interactions by capillary electrophoresis.
Drug-protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; alpha(1)-acid glycoprotein (AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, beta-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-frontal analysis is presented. Furthermore, the binding of these drugs to all plasmatic proteins is evaluated by using ultrafiltration and CE. The results indicate that the hydrophobic character of compounds seems to be the key factor on the interaction between cationic drugs towards proteins. In fact, hydrophobic basic drugs bind in great extension to HSA, while hydrophilic basic drugs present low interactions with proteins and bind especially to AGP.
Martínez-Gómez
María A
MA
Departamento de Química Analítica, Facultat de Farmacia, Universitat de Valencia, Burjassot, Valencia, Spain.
Sagrado
Salvador
S
Villanueva-Camañas
Rosa M
RM
Medina-Hernández
Maria J
MJ
D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D001798:Blood Proteins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D007741:Labetalol / Q000737:chemistry; D009961:Orosomucoid / Q000737:chemistry; D010640:Phenothiazines / Q000737:chemistry*; D010869:Pindolol / Q000737:chemistry; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D013843:Thiazines / Q000737:chemistry; D014462:Ultrafiltration
D000319:Adrenergic beta-Antagonists; D001798:Blood Proteins; D009961:Orosomucoid; D010640:Phenothiazines; D012709:Serum Albumin; D013843:Thiazines; C514701:etopropazine; D010869:Pindolol; D007741:Labetalol