Drug Metabolism and Metabolite Kinetics

Question 1

CLm

Answer 1

metabolic clearance (vol/time or vol/time/kg BW)

Question 2

CL(m)

Answer 2

clearance of metabolite (vol/time or vol/time/kg BW)

Question 3

The purpose of drug metabolism is the change the drug into a ___________.

Answer 3

polar (or water-soluble or hydrophilic) compound

Question 4

phase I reaction includes:

Answer 4

oxidation, reduction, and hydrolysis

Question 5

Phase II reactions includes:

Answer 5

glucuronidation, sulphation, acetylation, methylation, etc.

Question 6

What represents the biotransformation of a parent drug to its metabolite?

Answer 6

Metabolic clearance or metabolite formation clearance (CLm)

Question 7

What is the systemic clearance of a metabolite?

Answer 7

Clearance of metabolite (CL(m))

Question 8

fm represents the fraction of a dose in the systemic circulation that is converted to the metabolites.

Answer 8

True

Question 9

fm =

Answer 9

total amt of metabolites recovered/bioavailability x administered dose (Am/FxD)

Question 10

T/F - CLm may be part of CLh, but never be part of CLr and/or CLbile because CLr and CLbile characterize the excretion of unchanged drug in urine and bile, respectively.

Answer 10

True

Question 11

Metabolic clearance represents the ___________ and can be calculated as _________>

Answer 11

biotransformation of a parent drug to its metabolites; CLm=Am/AUC

Question 12

Clearance of metabolites represents the _____________ and can be determined as ______________.

Answer 12

systemic clearance of a metabolite; CLm=Dm/AUCm

Question 13

Total amount of metabolites excreted is determined in ___________.

Answer 13

both urine and fecal samples

Question 14

Following the IV administration of 100mg of DrugA, a total of 20mg of its metabolites were covered in urine and feces. Calculate fm

Answer 14

fm=Am/(FD) = 20/(1100) = 0.2

Question 15

Following the oral administration of 100mg of Drug B, the amount of metabolites recovered in urine and feces was 15mg, respectively. It is known that Drug B has an oral bioavailability of 55%. Calculate fm

Answer 15

fm=Am/FD = (15+5)/(0.55100) = 0.364

Question 16

What is total Clearance?

Answer 16

Total clearance is the sum of clearance in individual organs/tissues
CL = CLm + CLr +CLbile

Question 17

Km represents ____________ and has units of __________.

Answer 17

binding affinity of a drug for enzymes; amt/vol (or conc.

Question 18

Vmax represents _________ and has units of _________.

Answer 18

metabolic efficiency; amt/time

Question 19

When drug conc. equals Km, the rate of metabolism should be__________.

Answer 19

half of Vmax

Question 20

T/F - Both Vmax and Km are dependent of substrate conc. (C), but may be altered when the biotransformation environment changes, or in the presence of enzyme inducers or inhibitors.

Answer 20

F - they are independent of one another

Question 21

inhibition of drug metabolism is the major cause of…

Answer 21

reduced (unbound) clearance

Question 22

Inhibition can be generally categorized into …

Answer 22

competitive and noncompetitive inhibition

Question 23

When the drug conc. is doubled, Km should be __________ and Vmax should be _________.

Answer 23

unchanged; unchanged

Question 24

When the enzyme conc. is doubled, Km should be ________ and Vmax should be _______.

Answer 24

unchanged; doubled (Vmax is proportional to enzyme conc.)

Question 25

In the presence of a competitive inhibitor, Km should _______ and Vmax should __________.

Answer 25

increase; stay unchanged

Question 26

In the presence of a non-competitive inhibitor, Km should _________ and Vmax should ___________.

Answer 26

stay unchanged; decrease