Metabolite PK

Question 1

Parent drug fate

Answer 1

-in/active metabolite
-excreted in urine as parent drug

Question 2

Contribution of metabolites to drug response

Answer 2

-can affect PK of drugs and alter response

Question 3

Metabolite mechs

Answer 3

-inhibit CYP
-bind to plasma proteins
-have pharmacological activity
-toxicity

Question 4

Prodrugs

Answer 4

-drug with no pharma activity that is converted to an active metabolite in vivo

Question 5

Rate-limiting step

Answer 5

-most effects of metabolites are concentration-dependent
-need to understand formation and elimiation kinetics of metabolism
-slowest step
-defines PK profile

Question 6

Formation and elimination kinetics

Answer 6

drug A –(kf)–> metaboliteAm –(km)–> elimination

dAm/dt = kfA - KMAM
formation-elimation

Question 7

parent drug and metabolite concentration on graph when formation is slow and elimination is fast

Answer 7

-parallel-ish lines
-dec with each other

Question 8

parent drug and metabolite concentration on graph when formation is fast and elimination is slow

Answer 8

-parent drug steep dec
-intersects high metabolite curve

Question 9

info on metabolite kinetics

Answer 9

come from parent drug

Question 10

low k value

Answer 10

slow

Question 11

high k value

Answer 11

fast

Question 12

apparent half life of parent drug

Answer 12

use kf
-same as true half life

Question 13

true half life of parent drug

Answer 13

use kf
-same as apparent

Question 14

apparent half life of metabolite

Answer 14

use smaller k

Question 15

true half life of metabolite

Answer 15

use km

Question 16

formation rate-limited drug things

Answer 16

-true t1/2 of metabolite is SHORTER than t1/2 of parent drug
-apparent t1/2 of metabolite SIMILAR to t1/2 parent
-kf«km
-typical of most drugs

Question 17

elimination rate-limted drug things

Answer 17

-apparent and true t1/2 is LONGER than t1/2 parent
-kf»km
-typical of prodrugs
-graph intersects

Question 18

CYP inducer effect on parent drug and metabolite half life in formation rate-limited

Answer 18

-decreases both
-think parallel lines

Question 19

Css in formation rate-limited

Answer 19

-determined by t1/2
-same for metabolite and parent drug

Question 20

Css in elimination rate-limited

Answer 20

-determined by t1/2
-LONGeR for metabolite than parent drug bc longer t1/2

Question 21

Metabolite PK after ORAL dosing

Answer 21

-might have high first pass effect
-high metabolite to parent ratio compared to IV

Question 22

When ORAL drugs have high EH and metabolite is INactive

Answer 22

-concentration of parent correspond to effect
-IV leads to quicker response
-low F of drug requires higher dose

Question 23

When ORAL PROdrug with high EH

Answer 23

-shorter onset
-more intense response after oral than IV
-low F of PROdrug does not mean poor therapuetic effect