1. Study Aids Anki Flash cards – Content that you need to know for the tests. MS Excel sheet with Calculations

2. PHARMACOKINETIC BASICS Lecture #2

4. Factors in Measuring Systemic Exposure Sites of Measurement (Where?) Unbound [Drug] Exposure-Time Profile Observation Period

5. Exposure-Time Profile In addition to the concentration, what other factor should we consider with exposure?

6. Sites of Measurement Invasive – Whole Blood, Plasma and Serum Unbound Drug Concentration and Fraction Unbound Non-invasive – Breath – Milk – Saliva – Feces – Urine

7. Chemical Purity/Enantiomers anticoagulant stimulant Decreases Rapidly [drug] very low

8. Active Metabolites and Prodrugs

9. Sites of Administration Intravascular  Systemic Circulation – Intravenous (IV) – Intra-arterially (IA) Extravascular  Absorption  Systemic Circulation – Buccal (Between Cheek and Gum) – Intradermal (ID) – Intramuscular (IM) – Oral – Pulmonary (Inhalation) – Subcutaneous (Subcut, Fat under Skin) – Rectal – Sublingual (SL, under the tongue)

10. Typical Exposure-Time Profiles Intravascular Extravascular Lag due to absorption [Drug] plasma

11. Parenteral Administration Restricted to Injected – Intravascular – Intramuscular – Subcutaneous

13. How a drug ends up- Drug Disposition (i.e. Amount Absorbed) Excreted Metabolite

14. Terms Elimination – Drug Metabolism – Amount/time (mg/hr) Excretion – Drug Removal from the Body – Amount/time (mg/hr) Clearance – Volume/time (L/hr)

15.  [Drug] = [Drug] in –[Drug] out  Drug Drug In Drug Out

17. Representing PK Equations Physiologic Models Compartment Models

18. Equations Why?

19. Physiologic Models

20. Compartmental Models

21. ADME

22. Systematic Absorption First Pass Loss Systemic Circulation Bioavailability (F)

23. Enterohepatic Cycle: Drugs Recycled

24. PK Terms Maximum Concentration (C max ) Maximum Time (t max ) Area Under the Curve (AUC)

25. C max and t max C max t max

26. What factors determine how much exposure that you have to a “poison”? systemic exposure = How long * How much [Drug] plasma time Systemic Exposure How long How much

27. What factors determine how much exposure that you have to a drug? AUC = How long * How much [Drug] plasma time Area Under the Curve (AUC) How long How much

28. Area Under the Curve (AUC) t max AUC (µg/L)*hr

29. Area Under the Curve

30. Drug Plasma After Intravenous (IV) Bolus Dose C(0) k=rate (/hr)

31. Drug Plasma After Intravenous (IV) Bolus Dose C(0) AUC C max and t max ?

32. Trapezoid Area a b c

33. CiCi tftf titi CfCf time [Drug]

34. Drug Plasma After Intravenous (IV) Bolus Dose C(0)

35. Drug Plasma After Intravenous (IV) Bolus Dose C(0) CtCt

36. Drug Plasma After Intravenous (IV) Bolus Dose Only C(0) Only works when the curve is shaped like this.