complexex part10

Drug-protein binding
The binding of drugs to proteins contained in the body can influence their action in a number of ways. Proteins may (a) facilitate the distribution of drugs throughout the body, (b) inactivate the drug by not enabling a sufficient concentration of free drug to develop at the receptor site, or (c) retard the excretion of a drug. The interaction of a drug with proteins may cause (a) the displacement of body hormone, (b) a configurational change in the protein, the structurally altered form of which is capable of binding a coadministered agent, or (c) the formation of a drug-protein  complex that itself is biologically active. Among the plasma proteins, albumin is the most important owing to its high concentration relative to the other proteins and also to its ability to bind both acidic and basic drugs. Another plasma protein, ?1-acid glycoprotein, has been shown to bind numerous drugs; this protein appears to have greater affinity for basic than for acidic drug molecules.
Binding equilibria
 The interaction between a group or free receptor, P in a protein and a drug molecule D    can be written as
 The equilibrium constant, disregarding the difference be¬tween activities and concentrations,   
Where K is the association constant, [P] is the concentra¬tion of the protein in terms of free binding sites, [Dfree] is the concentration, usually given in moles, of free drug, some¬times called the ligand, and [PD] is the concentration of the protein-drug complex. K varies with temperature and would be better represented as K(T); [PD], the symbol for bound drug, is sometimes written as [Db], and [D], the free drug, as [Df].
If the total protein concentration is designated as [Pt], we can write  
Substituting the expression for [P] from equation (11-32) into (11-31) gives
 Let r be the number of moles of drug bound, [PD], per mole of total protein, [Pt]; then r = [PD]/[Pt], or
 The ratio r can also be expressed in other units, such as mil¬ligrams of drug bound, x, per gram of protein, m. Expression (11-36) can be con¬verted to a linear form, convenient for plotting, by inverting it:
 If v independent binding sites are available, the expression for r, equation (11-36), is simply v times that for a single site, or
and equation (11-37) becomes
Equation (11-39) produces what is called a Klotz reciprocal Plot.
An alternative manner of writing equation (11-38) is to rearrange it first to
Data presented according to equation (11-41) are known as a Scatchard plot.
Equilibrium dialysis (ED) and Ultrafiltration (UF)
A number of methods are used to determine the amount of drug bound to a protein. Equilibrium dialysis, ultrafiltration, and eleetrophoresis are the classic techniques used, and in recent years other methods, such as gel filtration and nuclear magnetic resonance, have been used with satisfactory results.