1. ــــــــــــــ February 17 th, 2016 415 PHT - PRACTICAL Pharmacokinetic Basic Calculations Dr. Ahmed Alalaiwe

2. After this lecture, you will be able to: Calculate the rate of elimination (Ke) Get familiar with different methods of calculating AUC Memorize the units of different PK parameters Objectives

3. Elimination Rate Constant (Ke) overall elimination rate constant describing removal of the drug by all elimination processes including excretion and metabolism Ke

4. Proportionality constant relating the rate of change drug concentration and concentration It describes as : Ke = - dCp/dt Cp Ke

6. Equation: Unit of Ke: Ke

7. Examples: DrugKe (1/hour) (hour -1 ) Acetaminophen0.28 Diazepam0.021 Digoxin0.017 Gentamicin0.35 Lidocaine0.43 Theophylline0.063 Ke

8. Cp, Ke and time relationship Ke

9. Area Under the Plasma Curve (AUC) AUC

10. Can be calculated by: Trapezoid method Segments method AUC

11. AUC 2-3 = Cp 2 + Cp 3. ( t 3 – t 2 ) 2 Trapezoid Method

12. The first segment can be calculated after determining the zero plasma concentration Cp 0 by extrapolation AUC 0-1 = Cp 0 + Cp 1. t 1 2 Trapezoid Method

13. final segment can be calculated from t last to infinity: Trapezoid Method

15. TimeConc 0Unknown 171 250 335 425 612 86.2 103.1 Exercise

16. Calculate Ke: ln(x)=2.303. log(x) Time ln (Conc) 0Unknown 14.26 23.91 33.55 43.21 62.48 81.82 101.13 TimeConc 0Unknown 171 250 335 425 612 86.2 103.1 Exercise

17. Slope = = - 0.34 1/time Extrapolation of Cp 0 Cp = 71 Ke = -0.34 Cp0 = 100 Exercise

18. Calculation of first segment: AUC 0-1 = Cp 0 + Cp 1. t1 2 = (100 + 71)/2. 1 = 85.5 Calculation of last segment: AUC 0-∞ = Cplast / K = 3.1 /0.34 = 9.11 timeconcAUC 0100 17185.5 25060.5 33542.5 42530 61237 86.218.2 103.1 = Cp last 9.3 ??? Exercise

19. Total AUC: timeconcAUC 0100 17185.5 25060.5 33542.5 42530 61237 86.218.2 103.19.3 9.1 = AUC last total292.1 Exercise

20. mass. time / volume mg.hr/L Units

21. A graph of log A versus t will yield a straight line The y intercept will be log A 0 The slope of the line will be –k/2.3 Similarly, a graph of log C versus t will yield a straight line. The y intercept will be log C 0, and the slope of the line will be –k/2.3 First Order

22. Homework