Biomaterial Database

Cicletanine binding to human plasma proteins and erythrocytes, a particular HSA-drug interaction. 1988

R Zini, and D Morin, and P Jouenne, and J P Tillement

Laboratorie Hospitalo-Universitaire de Pharmacologie, Creteil.

The binding of cicletanine to human serum, isolated proteins and red blood cells was studied in vitro by equilibrium dialysis. Our results show this drug is highly bound to serum (97.3%) at therapeutic levels. No saturation to the binding sites was seen. Human serum albumin was shown to mainly responsible for this binding (93.5%) with a saturable process characterized by one binding site with a moderate affinity (K = 75800 M-1) and a non saturable process with a low total affinity (nK = 6400 M-1). Like many basic lipophilic drugs, cicletanine showed a saturable binding to alpha-1-acid glycoprotein with one site and a moderate affinity (K = 38,800 M-1). Its binding to lipoproteins and red blood cells was weak and non saturable. Over the range of therapeutic concentrations, the unbound fraction in blood remains constant (3.6%). Moreover, interactions were studied using bilirubin and non esterified fatty acids at pathological concentrations and these endogenous compounds did not alter cicletanine binding human serum or to human serum albumin likewise cicletanine shared the diazepam-site on HSA but no inhibition could take place between cicletanine and the drugs sharing the same binding site in serum at therapeutic levels.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008074	Lipoproteins	Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.	Circulating Lipoproteins,Lipoprotein,Lipoproteins, Circulating
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D003975	Diazepam	A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004232	Diuretics	Agents that promote the excretion of urine through their effects on kidney function.	Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000889	Anti-Arrhythmia Agents	Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.	Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic