Drug Metabolism and Metabolite Kinetics Flashcards
CLm
metabolic clearance (vol/time or vol/time/kg BW)
CL(m)
clearance of metabolite (vol/time or vol/time/kg BW)
The purpose of drug metabolism is the change the drug into a ___________.
polar (or water-soluble or hydrophilic) compound
phase I reaction includes:
oxidation, reduction, and hydrolysis
Phase II reactions includes:
glucuronidation, sulphation, acetylation, methylation, etc.
What represents the biotransformation of a parent drug to its metabolite?
Metabolic clearance or metabolite formation clearance (CLm)
What is the systemic clearance of a metabolite?
Clearance of metabolite (CL(m))
fm represents the fraction of a dose in the systemic circulation that is converted to the metabolites.
True
fm =
total amt of metabolites recovered/bioavailability x administered dose (Am/FxD)
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.
True
Metabolic clearance represents the ___________ and can be calculated as _________>
biotransformation of a parent drug to its metabolites; CLm=Am/AUC
Clearance of metabolites represents the _____________ and can be determined as ______________.
systemic clearance of a metabolite; CLm=Dm/AUCm
Total amount of metabolites excreted is determined in ___________.
both urine and fecal samples
Following the IV administration of 100mg of DrugA, a total of 20mg of its metabolites were covered in urine and feces. Calculate fm
fm=Am/(FD) = 20/(1100) = 0.2
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
fm=Am/FD = (15+5)/(0.55100) = 0.364
What is total Clearance?
Total clearance is the sum of clearance in individual organs/tissues
CL = CLm + CLr +CLbile
Km represents ____________ and has units of __________.
binding affinity of a drug for enzymes; amt/vol (or conc.
Vmax represents _________ and has units of _________.
metabolic efficiency; amt/time
When drug conc. equals Km, the rate of metabolism should be__________.
half of Vmax
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.
F - they are independent of one another
inhibition of drug metabolism is the major cause of…
reduced (unbound) clearance
Inhibition can be generally categorized into …
competitive and noncompetitive inhibition
When the drug conc. is doubled, Km should be __________ and Vmax should be _________.
unchanged; unchanged
When the enzyme conc. is doubled, Km should be ________ and Vmax should be _______.
unchanged; doubled (Vmax is proportional to enzyme conc.)
In the presence of a competitive inhibitor, Km should _______ and Vmax should __________.
increase; stay unchanged
In the presence of a non-competitive inhibitor, Km should _________ and Vmax should ___________.
stay unchanged; decrease
