Pharmacokinetic of cdds
- 1. Prepared By:- Dheeraj Kumar M.S.(Pharmaceutics) 443/MS-PE/17 4 June 2018 1
- 2. Contents Introduction Absorption Distribution Metabolism Excretion Pharmacokinetic Prameters Pharmacokinetic models 4 June 2018 2
- 3. PHARMACOKINETICS Kinetics of drug absorption, distribution, metabolism and excretion (KADME) and their relationship with pharmacological and therapeutical response. Pharmacokinetics = pharmackon + kinetikos (drug) (moving) Stduy of movement of drug inside the body. Pharmacokinetics is what body does to the drug. 4 June 2018 3
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- 6. Absorption Ideal CRDDS should release the complete drug and the released drug should be completely absorbed The fraction of drug absorbed from the system can be lower than the expected due to: -degradation of drug. Eg- Penicillin G -site-specific, dose-dependent absorption, -poor water solubility -small partition coefficient. 4 June 2018 6
- 7. Distribution Distribution refers to the reversible transfer of drug from one location to another inside the body. Depends on affinity of drug to bind with plasma proteins and ability of drug to pass through tissue membranes. Apparent volume of distribution (Vd) is defined as the hypothetical volume of body fluids to which a drug is dissolved or distributed. 4 June 2018 7
- 8. Metabolism Metabolism of a drug is either an inactivation, of an active drug or conversion of an inactive drug to an active metabolite or active drug with active metabolites. There are two factors related to metabolism of drug which restrict the design of CRDDS: Drugs possessing variations in bioavailability due to first-pass effect or intestinal metabolism are not suitable for sustained/controlled drug delivery. For chronic administration, drugs that are capable of either inducing or inhibiting enzyme synthesis, are poor candidates for controlled delivery systems due to difficulty in maintaining uniform blood levels. 4 June 2018 8
- 9. Elimination Ir-reversible removal of drug from the body. Time taken for the amount of drug in body by one half is called elimination half life. The loss of drug across an organ is viewed as clearance. Clearnce can be presented in terms of eliminating oragn such as hepatic clearance, renal clearance etc. 4 June 2018 9
- 10. Pharmacokinetics Parameters Elimination half life Protein binding of drug Apparent volume of distribution(Vd) Cmax Tmax Area under the concentration time curve(AUC) Clearance Absolute Bioavailability Relative Bioavailability 4 June 2018 10
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- 12. Elimination half life: It is the time required to reduce the concentration in plasma to one half of the initial concentration. Independent of the amount of drug in the body. Depends on Clearnce and Volumne of distribution. The shorter the half life greater will be the amount of drug to be incorporated in the delivery system. Drugs with t1/2 of 3-4 hours are best candidate for controlled drug delivery system. 4 June 2018 12
- 13. Cont… Half life determination 4 June 2018 13
- 14. Protein Binding of Drug 4 June 2018 14
- 15. Apparent volume of distribution(Vd) Hypothetical volume of body fluids into which a drug is distributed Vd=X/C Where X=Amount of drug in body C=Plasma drug concentartion 4 June 2018 15
- 16. Drugs which binds to plasma proteins have low Vd while the drugs which binds to extravascular tissues have high Vd. For Example:- Warfarin(10 liters) , Chloroquin(15000 liters) Fluids compartments of an adult 4 June 2018 16
- 17. Area under the concentration time curve(AUC): AUC is the measure of quantity of drug in the body. AUC is generally determined by trapezoidal rule. Absolute bioavailability and relative bioavailability are caluculated from AUC. 4 June 2018 17
- 18. Absolute Bioavailability:- compares the bioavailability of the active drug following extravascular administration with the bioavailability of the same drug following intravenous administration 4 June 2018 18
- 19. Relative Bioavailability:- A type of comparative bioavailability assessment Relative bioavailability studies compare two drug product formulations 4 June 2018 19
- 20. Clearance : Clearance is the hypothetical volume of body fluids containing drug from which the drug is cleared completely in a specific period of time. It is expressed in ml/min or litre/hour. 4 June 2018 20
- 21. Mean residence time: It is the mean time a drug molecule reside in the body It is calculated from AUC and AUMC MRT = AUMC/AUC 4 June 2018 21
- 22. Pharmacokinetic models A model is a hypothesis that employs mathematical terms to concisely describe quantitative relationships. Used for determination for various pharmacokinetic parameters A pharmacokinetic function relates an independent variable to a dependent variable. 4 June 2018 22
- 23. Pharmacokinetic models Compartmental models Catenary models Mammillary models Physiological models 4 June 2018 23
- 24. Catenary model Various compartments are joined to each other in series like the compartments of train. This model is rarely used. 4 June 2018 24
- 25. Mammillary model Most common model used in pharmacokinetics. One or more peripheral compartments connected to central compartment. 4 June 2018 25
- 26. Physiological model Pharmacokinetic models based on known anatomic and physiologic data. The model would potentially predict realistic tissue drugconcentrations, which the two-compartment model fails to do. Unfortunately, much of the information required for adequately describing a physiologic pharmacokinetic model are experimentally difficult to obtain. 4 June 2018 26
- 27. THANK YOU 4 June 2018 27