protein binding

1. By
P SANDHYA
B PHARM III SEM (2017-21)
TRINITY COLLEGE OF PHARMACEUTICAL SCIENCES
PEDDAPALLI, TELANGANA

2.  PROTEINBINDING:-
 Proteins such as albumin and globulin are
present in the Among these, the level of
albumin is very high and plays a common role
in the drug protein binding.
 Alpha-acid glycoprotein (a-AGP) levels
very low in normal healthy population. But,
in the diseased state as myocardial
infarction, AGP levels increases.

3.  When drugs in blood, it is possible that these
macromolecules (proteins) bind drugs Albumin
binds both acidic and basic drugs.
 AGP binds most of the basic drugs rather than
acidic drugs.
 Globulins bind drug to a little extent.
 Globulin interactions are important in case
of immuno globulins crucial Drug protein
binding influences the pharmacokinetics,
pharmacodynamics, drug action in various
ways.

4. 1. Drug distribution :-
 Protein binding decreases the distribution of
drugs. The protein-bound drug is big in size which
cannot easily cross cell membranes and therefore,
restricts to the blood pool.
 Only free (unbound) drug can pass through the cell
membranes and contributes to the tissue binding.
 The higher the protein binding, the lower the tissue
distribution.
 Tissue distribution is expressed in terms of volume
of distribution. For example, phenylbutazone bound
to protein to the extent of 96% .

5. 2. Metabolism :-
 Protein binding decreases the metabolism
of drugs and enhances the biological half
life.
 Only that fraction of drugs which is free
can get metabolized. Examples are
phenylbutazone and sulfonamides.

6. 3. Excretion :-
 Protein binding decreases the renal excretion of drugs
and enhances the biological half life. Only the free drugs can get excreted
through glomerular filtration.
 For example, tetracyclines are excreted mainly by glomerular
filtration. drugs bind to proteins and results in decreased renal
excretions.

7. 4. Drug action :-
 Protein binding inactivates the drug, because of sufficient
concentration of drug cannot be built up in the receptor site for
action.
 Example is naphthoquinones.

8. r = {PD} / {P1} = K{Df} / 1 + K{Df}
 This Equation is one of the forms of the
Langmuir adsorption isotherm .
 It is useful in predicting the drug protein binding
1+KIDA provided binding is an adsorption
process.
 The above equation ,if the protein contains one
binding site. If v is the number of independent
binding sites available, then 'r' in above equation
can be written as,
r = v. K{Df} / 1 + K{Df}

9. The graph presented according to equation is
called a Klotz double reciprocal plot .
The association constant may be determined
from the slope, if the value of v' is known double
protein reciprocal Slope.