PKPD Exam 3

Question 1

bioavailability of digoxin tablets

Answer 1

f = 0.7

Question 2

bioavailability of digoxin elixir

Answer 2

f = 0.8

Question 3

bioavailability of digoxin lanoxicaps

Answer 3

f = 1

Question 4

average volume of digoxin

Answer 4

7.3 L/kg

Question 5

therapeutic range (css,av) for digoxin

Answer 5

0.5-2.0 ng/mL (mcg/L)

Question 6

why is pk optimization needed for digoxin

Answer 6

-high interpatient variability in disposition
-low TI
-poor accuracy in predicting PK parameters from patient characteristics

Question 7

after how many hours are collected digoxin concentrations considered the Css,av concentration

Answer 7

6 hours

Question 8

what is the specific activity of anti-digoxin immune fab

Answer 8

0.8

Question 9

why is there a maximum infusion rate for phenytoin sodium

Answer 9

avoid hypotension due to cardiac suppression

Question 10

what is the water soluble ester prodrug of phenytoin that avoids injection problems and can be administered more rapidly

Answer 10

fosphenytoin

Question 11

why is IM phenytoin sodium not recommended

Answer 11

some precipitates resulting in prolonged erratic absorption, painful

Question 12

phenytoin is a weak acid with limited water solubility, so absorption is…..

Answer 12

slow, peaks delayed several hours

Question 13

phenytoin is primarily bound to

Answer 13

albumin in the plasma

Question 14

concentrations of phenytoin needed to be adjusted to account for

Answer 14

altered protein binding
ESRD

Question 15

which drug displaces phenytoin from plasma albumin and needs to be considered to adjust concentration

Answer 15

valproate

Question 16

how is phenytoin primarily cleared

Answer 16

hepatic metabolism by CYP2C9

Question 17

what type of PK does phenytoin follow

Answer 17

nonlinear–> number of drug saturates the enzymes ability to metabolize the drug

Question 18

therapeutic range of phenytoin

Answer 18

10-20 mg/L of total phenytoin

Question 19

what is the Vd of phenytoin (estimated before data)

Answer 19

0.65 L/kg

Question 20

what is the Vmax of phenytoin (estimated before data)

Answer 20

7 mg/kg/day

Question 21

what is the Km of phenytoin (for estimation before data, or when 1 dosing regimen is available)

Answer 21

4 mg/L

Question 22

what is the absorption of carbamazepine

Answer 22

-rate varies between dosage forms
-may have saturable absorption, high doses may have reduced F
-IR- slow, erratic, unpredictable due to slow dissolution (secondary peaks may occur)

Question 23

should IR or ER carbamazepine be taken with food

Answer 23

IR & ER tabs– yes
ER caps– with or without

Question 24

distribution of carbamazepine

Answer 24

rapid and uniform
binds to albumin and AAG

Question 25

how is carbamazepine primarily cleared

Answer 25

hepatic metabolism by CYP3A4

Question 26

what DDIs are carbamazepine responsible for

Answer 26

potent enzyme inducer- enhances metabolism of many drugs

Question 27

carbamazepine is an autoinducer, so it...

Answer 27

induces its own metabolism

Question 28

what is the therapeutic range of carbamazepine

Answer 28

4-12 mg/L

Question 29

what concentration of carbamazepine is associated with AEs

Answer 29

>15 mg/L

Question 30

how is dosing initiated in carbamazepine

Answer 30

-start at 1/4 to 1/3 of the desired maintenance dose -increase by a similar amount ever 2-3 weeks until desired dose reached

Question 31

when can therapeutic effect and steady state be assessed in carbamazepine

Answer 31

2-3 weeks after final dosing increase

Question 32

what is the benefit of gradual exposure of carbamazepine

Answer 32

-tolerance of AEs -allows liver enzyme induction and CL increases to occur over the 6-12 week period

Question 33

absorption of valproic acid

Answer 33

rate depends on dosage form, delay may be 1-6 hours

Question 34

how does food affect absorption of valproic acid

Answer 34

can decrease the rate of absorption time to achieve peak may be delayed 3-8 hours

Question 35

what is the distribution of valproic acid

Answer 35

Vd is relatively small

Question 36

what is valproic acid bound to? is it saturable

Answer 36

highly bound to albumin, binding is saturable

Question 37

how is valproic acid cleared

Answer 37

primarily eliminated by the liver

Question 38

what concentration dependent change occurs with valproic acid? what does this reflect

Answer 38

CL --> higher CL at higher concentrations higher CL may reflect saturable protein binding

Question 39

what DDIs is valproic acid responsible for

Answer 39

enzyme inhibitor subject to enzyme induction

Question 40

what is the target concentration of valproic acid

Answer 40

minimum trough: 40-50 mg/L seizure control improves with trough: 40-120 mg/L some may tolerate and benefit from >120 mg/L

Question 41

what is the typical maintenance dose of valproic acid

Answer 41

15 mg/kg/day

Question 42

what is the density of ethanol

Answer 42

0.78924 g/mL

Question 43

how is BAC provided

Answer 43

%w/v (g/dL)

Question 44

alcohol contents of beer

Answer 44

5% v/v 18mL/355mL

Question 45

alcohol contents of wine

Answer 45

12% 18mL/150mL

Question 46

alcohol contents of distilled beverages

Answer 46

40% 12mL/30mL

Question 47

how is gastric emptying affected by high concentrations of EtOH? how does this affect absorption?

Answer 47

gastric emptying inhibited by high concentrations complete absorption may require 2-6h

Question 48

what is distribution of ethanol

Answer 48

very rapid, V ~ V of total body water (0.6L/kg)

Question 49

how is ethanol primarily metabolized

Answer 49

oxidized metabolized to acetylaldehyde by alcohol dehydrogenase, then further metabolized to acetyl CoA

Question 50

what type of PK does ethanol follow

Answer 50

nonlinear --> elimination is saturable