This document discusses protein binding of drugs in the body. It explains that bound drugs are pharmacologically inert and that various bonds like hydrogen bonds, hydrophobic bonds, and ionic bonds are responsible for binding. It then discusses in detail binding to blood components like plasma proteins (albumin, alpha-1 acid glycoprotein, lipoproteins, globulins), blood cells, and various tissues. Finally, it covers factors that affect protein binding like drug properties, protein/tissue characteristics, drug interactions, and patient factors. It also defines volume of distribution and distinguishes between apparent and real volume of distribution.

1. Protein binding of drugsMahesh Thube PatilM.Pharm Sem. II,Dept. Of P’ceu,Government College of Pharmacy, Aurangabad,Maharashtra, India.maheshethube@gmail.com

2. IntroductionBound Drug is Pharmacodynamicaly inert.

3. Binding: Half life of drug.

4. Bonding : Hydrogen bond, Hydrophilic bond, ionic bond, Vander Walls bond.

5. Irreversible bonding : Covalent bonding : responsible for the Carcinogenicity or Tissue toxicity.GCP Aurangabad.Friday, October 01, 20102

6. Binding Of DrugGCP Aurangabad.Friday, October 01, 20103

7. A) Binding to Blood ComponentsFriday, October 01, 2010GCP Aurangabad.4I) Plasma Protein Binding of drug:Reversible

8. Order : Albumin > α1 AG > Lipoproteins > Globulins.

9. Involves binding to : Human serum Albumin.α1 Acid Glycoprotein,Lipoproteins,Globulins

10. 1. Binding to HSAFriday, October 01, 2010GCP Aurangabad.5Primary site:Secondary site:Bond: Hydrophobic bond.

11. 2. Binding to LipoproteinsBinding by: Hydrophobic Bond. Non-competative.

12. Mol wt : 2-3 lacks Dalton.

13. Binded drug dissolves in Lipid core.

14. Lipid Core composed of :Inside: Triglycerides, cholesterol esters,Outside: Appoprotein.E.g :Acidic: Diclofenac.Neutral: Cyclosporine ABasic: Chlorpromazine. Friday, October 01, 2010GCP Aurangabad.6

15. 3. Binding to α1 Acid GlycoproteinFriday, October 01, 2010GCP Aurangabad.7 Binding by: Hydrophobic bonds.

16. E.g. : Basic Drugs: Imipramine, Amytriptyline, Lidocaine.4. Binding to Globulin

17. II )Binding To Blood CellsFriday, October 01, 2010GCP Aurangabad.840 % of Blood comprises of blood cellsMajority is RBCs: 500 times more diameter as Albumin.RBC Components that binds to drug:

18. B) Tissue Binding Of Drug:Friday, October 01, 2010GCP Aurangabad.9Importance : 1. Apparent Vd. 2. Localization of drug at specific site : so biological half life.Factors affecting : Lipophilicity, structural feature of drug, Perfusion rate, pH difference.Binding Order : Liver > Kidney > Lungs > Muscle.