Warfarin PK/PD

Question 1

Maintenance dose of warfarin

Answer 1

1.5-12 mg/day

Question 2

Bioavailability of warfarin

Answer 2

> 90%

Question 3

Tmax of warfarin

Answer 3

1-2 hours

Question 4

Vd of warfarin

Answer 4

0.08-0.12 L/kg

aka SMALL Vd

Question 5

Protein binding of warfarin

Answer 5

> 99%

Question 6

Plasma concentration of warfarin

Answer 6

1.5-8 mmol/L

Question 7

Which enantiomer has a longer half-life?

Answer 7

R-warfarin

Question 8

Which enantiomer has a lower CL?

Answer 8

R-warfarin

Question 9

Active form of warfarin

Answer 9

S-warfarin

Question 10

Target-mediated drug disposition definition

Answer 10

Binding to the target influences the PK and disposition of the drug

Question 11

PK characteristics of TMDD (6 things)

Answer 11

Nonlinear Vd and CL
Steep distributive phase for low doses
Long terminal elimination
Dose proportional on MD
Time lag to Css with low dose IV infusion
Low doses=longer to get to Css

Question 12

Warfarin is ? dependent.

Answer 12

CONCENTRATION

Question 13

Is there saturable tissue binding with warfarin?

Answer 13

Yes

Question 14

Is warfarin a low or high extraction drug

Answer 14

Low

Question 15

S-warfarin is metabolized by what CYP enzyme?

Answer 15

2C9

Question 16

R-warfarin is metabolized by what enzymes

Answer 16

1A1, 1A2, 2C19, 3A4, catechol-O-methyltransferase, ketoreductase

Question 17

Warfarin MoA

Answer 17

Inhibits the cyclic interconversion of vitamin K

Question 18

Warfarin’s indirect PD response

Answer 18

The peak response is delayed in relation to the concentration

Question 19

Clinical considerations of warfarin: Age

Answer 19

Increased age, decreased CL

Question 20

Clinical considerations of warfarin: genetic polymorphisms

Answer 20

CYP2C9 and VKORC1

Question 21

Clinical considerations of warfarin: body weight

Answer 21

Obese patients have decreased initial response

Question 22

Other clinical considerations of warfarin

Answer 22

Sex, DDIs, disease considerations, adherence, dietary intake of Vitamin K

Question 23

INR value for monitoring

Answer 23

2-3

Question 24

Pharmacogenetic testing for warfarin

Answer 24

Has either no or marginal usefulness in warfarin dosing

Question 25

Bayesian adaptive control of individual dosage regimens: components

Answer 25

1. Population PK or PK/PD model
2. Feedback measurements of drug concentrations and/or effects
3. Patient characteristics for model covariate relationships

Question 26

MoA of Eliquis, Xarelto, edoxaban

Answer 26

Inhibit factor Xa

Question 27

MoA of dabigatran

Answer 27

Inhibits Factor IIa