1. MECHANISTIC PHARMACOKINETICS: COMPARTMENTAL MODELS
Lecture 6
MECHANISTIC PHARMACOKINETICS: COMPARTMENTAL MODELS
Adv PK/PD 2006
Lecture 6

2. One Compartment Model
Model =V1, k10
Adv PK/PD 2006
Lecture 6

3. Two compartment model
Model =V1, k10, k12, k21 V2 = V1 k12 / k21 CL1 = V1 k10 CL2 = V1 k12
Adv PK/PD 2006
Lecture 6

4. Three compartment model
Model =V1, k10, k12, k21, k13, k31 V2 = V1 k12 / k21 V3 = V1 k13 / k31 CL1 = V1 k10 CL2 = V1 k12 CL3 = V1 k13
Adv PK/PD 2006
Lecture 6

5. Two Compartment Model A2 A1
Adv PK/PD 2006
Lecture 6

6. Two Compartment Model
Adv PK/PD 2006
Lecture 6

7. Two Compartment Model
Adv PK/PD 2006
Lecture 6

8. Three Compartment Model
Adv PK/PD 2006
Lecture 6

9. Three Compartment Model
Adv PK/PD 2006
Lecture 6

10. Population Pharmacokinetics
General rule for compartment models:
Estimate the volumes and clearances
These are NOT the underlying physical reality, by they come closer than other methods of parameterizing the model
Volumes and clearances are the most likely to be normally distributed
Adv PK/PD 2006
Lecture 6

11. Volume of Distribution at Steady State
By definition, at steady state: C1=C2 = Css
Adv PK/PD 2006
Lecture 6

12. Volume of Distribution at Steady State
However, the statement C1 = C2 = Css only holds when elimination is from the central compartment
If elimination occurs from compartment 2, then Vss is dependent on k20 and hence on clearance
Adv PK/PD 2006
Lecture 6

13. Saturable Elimination
Adv PK/PD 2006
Lecture 6

14. Saturable distribution
Saturable plasma and/or tissue protein binding eg ACE inhibitors.
CLu = unbound tissue clearance
Cu = unbound concentration
nPt = total number of binding sites in tissue
Ka = association constant of bound drug
Adv PK/PD 2006
Lecture 6

15. Saturable distribution
Adv PK/PD 2006
Lecture 6