PHRM 835 Exam 2 Metabolite Kinetics

Question 1

__________ can affect PK of parent drugs and alter pharmcologic response to the parent drug

Answer 1

metabolites

Question 2

what is the metabolite for zidovudine?

Answer 2

zidovudine triphosphate

Question 3

what enzyme converts irinotecan (inactive prodrug) to SN-38 (active metabolite)?

Answer 3

carboxyesterase

Question 4

what variable indicates metabolite formation rate?

Answer 4

kf

Question 5

what variable indicates elimination rate?

Answer 5

km

Question 6

if K &laquo_space;Km for IV bolus, metabolite elimination is _______ rate-limited

Answer 6

formation

Question 7

if K&raquo_space; Km for IV bolus, apparent metabolite elimination is _______ _______ rate-limited

Answer 7

metabolite elimination

Question 8

tolbutamide is a low Eh drug and its fe = 0. What would happen to half-life of tolbutamide when it is combined with rifampin, an inducer of CYP2C9 expression?

Answer 8

half life would decrease

(CL = fu * CLint; CLint increases, so CL increases;
CL = k * V; k goes up
t1/2 = 0.693/k)

Question 9

what would happen to half-life of hydroxytolbutamide when tolbutamide is combined with rifampin, an inducer of CYP2C9 expression?

Answer 9

decreased t1/2

Question 10

tolbutamide is an example of formation/elimination limited

Answer 10

formation

Question 11

methylprednisolone hemisuccinate is an example of formation/elimination limited

Answer 11

elimination

Question 12

metabolite PK after infusion, formation limited: time to reach steady state for metabolite is ____ parent drug

a. longer than
b. shorter than
c. same as

Answer 12

c. same as

Question 13

metabolite PK after infusion, elimination-limited: time to reach steady state for metabolite is _____ parent drug

a. longer than
b. shorter than
c. same as

Answer 13

a. longer than

Question 14

do you need more drug in an IV dose or an oral dose?

Answer 14

oral

Question 15

first pass effect and active metabolites: drugs that experience significant first pass effect (high Eh) show ____ metabolite-to-parent drug concentration ratio after oral administration compared to IV

a. high
b. low

Answer 15

a. high

Question 16

when drugs of high Eh are administered and the metabolites are inactive, the activity comes from

a. the metabolite
b. the prodrug

Answer 16

b. the prodrug

(ex. labetalol (active) -> labetalol glucuronide (inactive))

Question 17

when prodrugs of high Eh are administered, the activity comes from

a. the metabolite
b. the prodrug

Answer 17

a. the metabolite

(low F of prodrug means parent drug is converted to a lot of metabolite, which is what we want for prodrugs)

Question 18

true or false: drugs of high Eh are associated with low F. A prodrug that has a high Eh would exhibit minimal to no pharmacological activity after oral dosing

Answer 18

false