Protein act as carriers. The phenomenon of complex formation of drug is called Protein Binding Of Drugs.

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Presented by: Sk Rahabar.
Email:- skrahabar0@gmail.com
Division: Pharmaceutics
M.Pharm ,2nd semester
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
MAULANA ABUL KALAM AZAD UNIVERSITY OF TECHNOLOGY, WB

2.  Introduction.
 Mechanism of protein binding of drug’s.
 Classes of protein binding:-
1.Binding of drug to Blood Components.
2.Binding of drug to extravascular tissue.
 Factor’s affecting of protein binding of drugs.
 Significance of protein binding.
 Conclusion.
 References.
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3. Introduction
A drug in the body can interact with several tissue components.
The interacting molecules are generally macromolecules. such as Protein, DNA,
Adipose. The protein are particularly responsible for such an interaction.
The phenomenon of complex formation of drug with protein is called
Protein Binding of Drug.
Protein + Drug protein-drug complex.
 Binding of drug
falls into 2 classes:-
• Plasma proteins.
• Blood cells.
1.Blood
Components
• Protein.
• Fats.
• Bones etc.
2.Extra
vascular
tissue
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4. Mechanism of protein binding of drug’s.
Generally binding of drug to protein is two types reversible and
irreversible.
A. Reversible generally involves weak chemical bond such as:
 Hydrogen bonds.
 Hydrophobic bonds.
 Vander waal's forces.
B. Irreversible though rare, arise as a result of covalent binding
and often a reason for the carcinogenicity or tissue toxicity of
the drug.
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5. Drug
absorbed
Free drug in
plasma
Protein bound
drug in plasma
Pharmacologic
And
Therapeutic
Response
Receptor
No
pharmacologic
response,
therefore no
therapeutic
action
Figure:-Protein Drug Binding
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6. The binding of drugs to plasma proteins is reversible. The extent or order of
binding of drugs to various plasma proteins is:
Albumin > α1-acid Glycoprotein > Lipoproteins >
Globulins.
Site I :
warfarin and
azapropazone
binding site.
Site II : the
diazepam
binding site.
Site III :
digitoxin
binding site.
Site IV :
tamoxifen
binding site.
A. Binding of Drugs to Human Serum Albumin(HSA):
i. Plasma Protein-Drug Binding
• The human serum albumin (HSA), having a molecular weight of 65,000 & concentration
3.5-5% with a large drug binding capacity(59%).
• Both endogenous compounds such as fatty acid, bilirubin as well as drug binds to HSA.
• Four different sites on HSA have been identified for drug-binding…..
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7. •Molecular weight:44,000 dal and Concentration range: 0.04 to 0.1 g%.
•Binds to: basic drugs like imipramine, amitriptyline, nortriptyline, propranolol and
quinidine.
B. Binding of Drugs to Lipoproteins:
• Binding by: hydrophobic bond,
• The molecular weight: 2-34 lacks.
• Lipid core composed of: Inside:
triglycerides & cholesteryl esters,
Outside: apoprotein.
C. Binding of Drugs to α1-Acid Glycoprotein (AAG):
1. Chylomicrons
2.
Very low density
lipoproteins (VLDL)
3.
Low density lipoproteins
(LDL)
4.
High density lipoproteins
(HDL)
4 types of lipoproteins
D. Binding of Drugs to Globulins:
Globulin Synonym Binds to
1. α1-Globulin Transcortine
/corticosteroid binding globulin
Steroidal drugs, thyroxin &
cyanocobalamine
2. α2-Globulin Ceruloplasmin Vitamins A, D, E and K and cupric
ions.
3. ß1-Globulin Transferin Ferrous ions.
4. ß2-Globulin - Carotinoids
5. γ-Globulin - Antigens
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8. ii. Binding of Drugs to Blood Cells
• In blood 40% of blood cells of which major components is RBC (95%). The rate
extent of entry into RBC is more for lipophilic drugs.
• The RBC comprises of 3 components:-
a) Hemoglobin: It has a M.W. 64500 Dal. Drugs like Phenytoin, Phenobarbital bind to
haemoglobin
b) Carbonic Anhydrase: Drugs like Acetazolamide & Clorthalidone.
c) Cell Membrane: Imipramine & Chlorpromazine are reported to bind with RBC
membrane.
2. Binding of to extra vascular tissue protein
• the order of binding of extra vascular tissues is:
liver > kidney > lung > muscle.
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• Importance:
a) It increases apparent volume of distribution of drug.
b) Localization of a drug at a specific site in body.

9. Determination of protein drug
binding
1.Indirect
techniques:-
2.Direct
techniques:-
• Equilibrium dialysis
• Ultra centrifugation
• Ultra filtration
• Gel filtration
• Electrophoresis
• UV-Spectroscopy
• Fluorimetry
• HPLC
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10. 1. Drug-related factors:-
a) Physicochemical characteristics of the drug.
b) Concentration of drug in the body.
c) Affinity of a drug for a particular binding component.
2. Protein/tissue related factors:-
a) Physicochemical characteristics of the protein or binding agent.
b) Concentration of protein or binding component.
c) Number of binding sites on the binding agent.
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a) Competition between drugs for the binding site (displacement
interactions).
b) Competition between drug and normal body constituents.
c) Allosteric changes in protein molecule.
3. Drug interaction:-
4. Patient-related factors:-
a) Age.
b) Inter-subject variation.
c) Disease states.

11. Significance of protein/tissue binding of drug
1. Absorption:-
• As we know the conventional dosage form follow first order
kinetics. So when there is more protein binding then it
disturbs the absorption equilibrium.
2. Distribution:-
• A protein bound drug in particular does not cross the BBB ,
the placental barrier, the glomerulus.
• The protein binding decreases the distribution of drug.
3. Metabolism:-
• Protein binding decreases the metabolism of drugs &
enhances the biological half life.
• Only unbound fraction get metabolized.
• E.g. Phenylbutazone & Sulphonamide.
4. Elimination:-
• Only unbound drugs is capable of being elimination.
• Protein binding prevent the entry of drug to the metabolizing
organ (liver) & to glomerulus filtration.
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12. 5. Systemicsolubility of drug:-
• Lipoprotein act as vehicle for hydrophobic drug like steroids ,heparin, oil
soluble vit.
6. Drug action:-
• Protein binding inactivates the drugs because sufficient concentration of
drug can not be build up in the receptor site for section. E.g. Napthoquinone.
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13.  The phenomenon of complex formation of drug with protein is called as
Protein-Drug binding.
 The importance of such binding derives from the fact that the bound drug is
both pharmacokinetics as well as pharmacodynamically inert.
 Protein drug binding mainly categories into two types-
1. Binding of drugs to blood components.
2. Binding of drugs to extravascular tissue
protein, fats, and bones.
 Of all types of binding, the plasma-protein drug binding is most significant
and most widely studied.
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14. Brahmanar D.M.,Jaiswal S.B. , Biopharmaceutics and Pharmacokinetic;A
Treatise, 3rd Edition, Vallabh Prakashan, Pages:-117-139.
KD Tripathi , Essentials of MEDICAL PHARMACOLOGY , 7th Edition , jaypee
brothers medical publishers(P) Ltd. Pages:-10-37.
Basit AW, Trenfield SJ. 3D printing of pharmaceuticals and the role of
pharmacy. Drug discovery and development. The Pharmaceutical
Journal.[Internet]. 2022 Aug 25.
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