1. Phoenix WinNonLin Assignment Due Today Access Phoenix remotely.

2. Phoenix WinNonLin Assignment Due 8/31/15 Import Simulated Data in Phoenix, Plot it in Phoenix and put it into a MS Word document.

3. LOGARITHM REVIEW Lecture #4

4. History of Logs John Napier (1614) and Joost Burgi (1620) Why? Simplify astronomical calculations. Multiplication was a simplification of addition – 3 x 5 = 5+5+5 Powers are a simplification of multiplication – 5 3 = 5 x 5 x 5 Division is the opposite of Multiplication Logs are opposite to Powers

5. What do logs do? Allows you to see the relationship between things? Linear Scale Log Scale Makes curves straight.

6. Logs log base answer = power base power = answer Powers

7. Powers to Logs Powers VersionLog Version 10 2 =100log 10 100=2 3 2 =9log 3 9=2 e 3 =20.085log e 20.085=3 e -kt = Clog e C = -kt What is e? =~2.718 * derived from an infinite series.

8. Properties of Logs: Positive Logs Implicit assumption log = log 10 ln = log e Log 1 = 0 Log 10 = 1 Log 100 = 2

9. Property of Logs: Negative Logs Log 0.1 = -1 Log 0.01 = -2 Log 0.001 = -3

10. Properties of Logs

11. KINETIC CONCEPTS Lecture #4

12. Things you will learn Fractional elimination rate constant (k) Half-time (t 1/2 ) Mean residence time (MRT) Extraction ratio (E) Amount of Drug (A) Volume distribution (V) Clearance (CL)

13. Linear/Cartesian PlotSemilogarithmic plot Fractional Elimination Rate (k) = - slope Linear vs. Log

14. Linear/Cartesian Plot Fractional Elimination rate (k) = - slope Semilogarithmic Plot Which one has the higher rate? Linear vs. Log

15. Half-Life (t1/2) Time in which the [drug] is half the initial [drug]

16. Mean Residence Time (MRT) MRT = Average time that a molecule stays in the body

17. Concentration mg L mg/L C = [Drug] V = Volume Distribution

18. [Drug] Reservoir

19. [Drug] Reservoir Blood Flow (Q)

20. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted

21. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted [Drug] Extracted = C-C out Initial [Drug] = C

22. Extraction Ratio

23. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted How fast are drugs presented to the extractor (mg/hr)?

24. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted How fast are drugs eliminated by the extractor (mg/hr)?

25. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted What is the volume of blood with drug extracted per hour?

26. [Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted Clearance

27. Amount of Drug (A) in the Blood C = [Drug] (mg/L) V = Volume Distribution (L) A (mg) = C (mg/L) * V (L) Example C=100 mg/L V=5L, which is the average volume of blood A=C*V=500 mg of drug in the blood

28. Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 100 mg/L A=500 mg What is the V? 500 mg 5L A = Amount of Drug in the Blood (mg)

29. Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 50 mg/L A=250 mg What is the V? 250 mg Brain 250 mg 10 L A = Amount of Drug in the Blood (mg)

30. Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 2 mg/L A=10 mg What is the V? 10 mg Brain 490 mg 250 L A = Amount of Drug in the Blood (mg)

31. What does Volume Distribution (V) Tell Us? If V=~5L, tells us that the drug is primarily in the blood. If V>5L, that is typical. If V>>5L, tells us that the drug is distributed away from the blood. Can V<5L?. No.

32. CL, V and k Clearance (CL, units=L/hr) = Blood Volume of Drug Remove/hr Volume Distribution (V, units=L) What does k = 0.5 /hr mean?

33. CL, V and t 1/2 Time in which the [drug] is half the initial [drug]

34. Total CL, AUC and V Dose (mg) = CL (L/hr) * AUC ((mg*hr)/L) – IV bolus

35. Things you learned Fractional elimination rate constant (k) Half-time (t 1/2 ) Mean residence time (MRT) Extraction ratio (E) Amount of Drug (A) Volume distribution (V) Clearance (CL)