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Protein binding of drugs2003

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Mahesh Thube Patil
Mahesh Thube Patil

Protein binding of drugs

EducationHealth & MedicineTechnology
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Protein binding of drugs Mahesh Thube Patil M.Pharm Sem. II, Dept. Of P’ceu, Government College of Pharmacy, Aurangabad, Maharashtra, India. maheshethube@gmail.com
Introduction ,[object Object]
Binding: Half life of drug.
Bonding : Hydrogen bond, Hydrophilic bond, ionic bond, Vander Walls bond.
Irreversible bonding : Covalent bonding : responsible for the Carcinogenicity or Tissue toxicity.GCP Aurangabad. Friday, October 01, 2010 2
Binding Of Drug GCP Aurangabad. Friday, October 01, 2010 3
A) Binding to Blood Components Friday, October 01, 2010 GCP Aurangabad. 4 I) Plasma Protein Binding of drug: ,[object Object]
Order : Albumin > α1 AG > Lipoproteins > Globulins.
Involves binding to : Human serum Albumin. α1 Acid Glycoprotein, Lipoproteins, Globulins
1. Binding to HSA Friday, October 01, 2010 GCP Aurangabad. 5 Primary site: Secondary site: Bond: Hydrophobic bond.
2. Binding to Lipoproteins ,[object Object]
Mol wt : 2-3 lacks Dalton.
Binded drug dissolves in Lipid core.
Lipid Core composed of :Inside: Triglycerides, cholesterol esters, Outside: Appoprotein. ,[object Object],Acidic: Diclofenac. Neutral: Cyclosporine A Basic: Chlorpromazine. Friday, October 01, 2010 GCP Aurangabad. 6
3. Binding to α1 Acid Glycoprotein Friday, October 01, 2010 GCP Aurangabad. 7 ,[object Object]
E.g. : Basic Drugs: Imipramine, Amytriptyline, Lidocaine.4. Binding to Globulin
II )Binding To Blood Cells Friday, October 01, 2010 GCP Aurangabad. 8 40 % of Blood comprises of blood cells Majority is RBCs: 500 times more diameter as Albumin. RBC Components that binds to drug:
B) Tissue Binding Of Drug: Friday, October 01, 2010 GCP Aurangabad. 9 Importance : 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.

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Protein binding of drugs2003

  • 1. Protein binding of drugs Mahesh Thube Patil M.Pharm Sem. II, Dept. Of P’ceu, Government College of Pharmacy, Aurangabad, Maharashtra, India. maheshethube@gmail.com
  • 2.
  • 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, 2010 2
  • 6. Binding Of Drug GCP Aurangabad. Friday, October 01, 2010 3
  • 7.
  • 8. Order : Albumin > α1 AG > Lipoproteins > Globulins.
  • 9. Involves binding to : Human serum Albumin. α1 Acid Glycoprotein, Lipoproteins, Globulins
  • 10. 1. Binding to HSA Friday, October 01, 2010 GCP Aurangabad. 5 Primary site: Secondary site: Bond: Hydrophobic bond.
  • 11.
  • 12. Mol wt : 2-3 lacks Dalton.
  • 13. Binded drug dissolves in Lipid core.
  • 14.
  • 15.
  • 16. E.g. : Basic Drugs: Imipramine, Amytriptyline, Lidocaine.4. Binding to Globulin
  • 17. II )Binding To Blood Cells Friday, October 01, 2010 GCP Aurangabad. 8 40 % of Blood comprises of blood cells Majority is RBCs: 500 times more diameter as Albumin. RBC Components that binds to drug:
  • 18. B) Tissue Binding Of Drug: Friday, October 01, 2010 GCP Aurangabad. 9 Importance : 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.
  • 19. Cont… Friday, October 01, 2010 GCP Aurangabad. 10
  • 20.
  • 22. Cationic/Basic binds : AAG2. Concentration of Drug: 3.Drug protein/tissue affinity:Digoxine Affinity to cardiac muscle. B)Protein/Tissue Related: 1.Physicochemical Characteristics : Lipophilicity α binding. 2. Concentration Friday, October 01, 2010 GCP Aurangabad. 11
  • 23.
  • 24. Tamoxifen & Dicumarol binds to 10 & 20 sites of alb.
  • 25. Indomethacine binds to 3site.C) Drug Interaction: 1.Competition between Drugs for binding site. D1: Displaced Drug. D2: Displacer Drug. E.g. Adm. Of Phenylbutazone to Warfarine therapy patient, result in Hemorrhagic reaction. Friday, October 01, 2010 GCP Aurangabad. 12 D2 D2+P D1+P
  • 26.
  • 27. Free FFA level increased during conditions :
  • 28. Physiological C. (Fasting)
  • 29. Pathological C. (Diabetes, M.I)
  • 30. Pharmacological (Heparin & Caffeine adm.).
  • 31.
  • 32. Allosteric Modulators: are agents responsible.
  • 33. E.g. Aspirins acetylating of Lysine of Alb. So modifying capacity of NSAIDS binding. Friday, October 01, 2010 GCP Aurangabad. 13
  • 34. D) Patient Related: 1.Age: Neonates: Low Alb. content: more free drug. Young Infants: High dose of Digoxine due to large renal clearance. Elderly: Low Alb. : so more free drug. 2.Intersubject Variability: Due to Genetic & Environmental Factors. 3. Disease State: Friday, October 01, 2010 GCP Aurangabad. 14
  • 35.
  • 36. Different tissue have diff. conc. So Vd cannot have a true physiologic meaning.
  • 37. (Amount of drug in body) α( Conc. Of drug in plasma) X α C X = Vd. C Def: Hypothetical Vol. of body fluid into which drug is dissolved or distributed. It is Apparent Vd : Because : All parts of body equilibrated with drug do not have equal conc. Friday, October 01, 2010 GCP Aurangabad. 15
  • 38. Real Vd : has direct physiological meaning, Is related to body water. Friday, October 01, 2010 GCP Aurangabad. 16
  • 39. Markers used to measure Real Vd Friday, October 01, 2010 GCP Aurangabad. 17
  • 40.
  • 43. Presentation at ISPA Educational Workshop, Copenhagen.