Chapter 2: Pharmacokinetics (2) Prof.R.D.Ye 2012-09-12
Chapter 2: Pharmacokinetics (2) Prof. R.D. Ye 2012-09-12
Quantitative Pharmacokinetics To derive and use expressions for pharmacokinetic parameters,the first step is to establish a mathematical model that accurately relates the plasma drug concentration to the rates of drug absorption,distribution,and elimination.The one- compartment model is the simplest model of drug disposition,but the two-compartment model provides a more accurate representation of the pharmacokinetic behavior of many drugs
Quantitative Pharmacokinetics To derive and use expressions for pharmacokinetic parameters, the first step is to establish a mathematical model that accurately relates the plasma drug concentration to the rates of drug absorption, distribution, and elimination. The onecompartment model is the simplest model of drug disposition, but the two-compartment model provides a more accurate representation of the pharmacokinetic behavior of many drugs
One-compartment model One-compartment model Ka Ke Absorption Drug- Elimination D A One-compartment model: V1=X1/Co V1:Apparent volume of distribution X1:Amount of drug in the compartment Co:Drug concentration at initial time
One-compartment model: V1 = X1 / C0 V1: Apparent volume of distribution X1: Amount of drug in the compartment C0: Drug concentration at initial time One-compartment model
Two-compartment model Two-compartment model Blood Ka Ke Absorption Drug Elimination Kd Drug Tissues B Two-compartment model: Central compartment:Heart,lung,liver,kidney Peripheral compartment:Skin,muscle,fat tissue,etc. (1)Drug enters into the central compartment,(2)then distribute to peripheral compartment;(3)eventually,drug is eliminated from the central compartment
Two-compartment model Two-compartment model: Central compartment: Heart, lung, liver, kidney Peripheral compartment: Skin, muscle, fat tissue, etc. (1) Drug enters into the central compartment, (2) then distribute to peripheral compartment; (3) eventually, drug is eliminated from the central compartment
Drug distribution Apparent volume of distribution Plasma (4L) ● Interstitial fluid (10L) Intracellular fluid (28L) B Calculation of the Va 50.00 (/6w) Distribution phase (a) 5.00 0.50 C Elimination phase(B) 0.05 0.00 0 Time 500mg injected IV Va Dose 500 mg Co 5 mg/L =100L C