FPGEE Pharmacokinetics 5 — Questions and Answers
Question 1: A patient on warfarin (narrow therapeutic index, highly albumin-bound) is started on a second drug that also binds albumin avidly. What is the initial expected pharmacokinetic consequence?
- Decreased free warfarin concentration
- Transiently increased free warfarin concentration (Correct answer)
- Increased warfarin clearance
- No change because total warfarin is unchanged
Correct answer: Transiently increased free warfarin concentration
Displacement from albumin transiently increases free warfarin fraction, raising pharmacological effect until clearance of the newly freed drug re-establishes equilibrium.
Question 2: Which of the following best describes the concept of 'flip-flop' kinetics after extravascular drug administration?
- Absorption is faster than elimination, so elimination limits the terminal slope
- Absorption is slower than elimination, so absorption rate limits the terminal slope (Correct answer)
- Distribution is faster than absorption
- First-pass effect reverses the typical Cmax relationship
Correct answer: Absorption is slower than elimination, so absorption rate limits the terminal slope
Flip-flop kinetics occurs when absorption rate constant (ka) < elimination rate constant (ke), making the absorption process the rate-limiting step controlling the terminal plasma decline.
Question 3: Creatinine clearance is used clinically to estimate which parameter for drug dosing in renal impairment?
- Hepatic clearance
- Volume of distribution
- Glomerular filtration rate (GFR) (Correct answer)
- Plasma protein binding capacity
Correct answer: Glomerular filtration rate (GFR)
Creatinine clearance is a surrogate marker for GFR and is used to estimate renal drug elimination capacity for dose adjustments.
Question 4: After repeated dosing at steady state, peak and trough concentrations fluctuate around the average Css. What determines the magnitude of fluctuation?
- Bioavailability only
- The ratio of dosing interval to drug half-life (Correct answer)
- Volume of distribution only
- Plasma protein binding percentage
Correct answer: The ratio of dosing interval to drug half-life
Greater fluctuation occurs when the dosing interval is long relative to half-life; shorter intervals relative to half-life produce less peak-to-trough variation.
Question 5: A drug is administered as a prodrug that requires hepatic conversion to its active metabolite. In severe hepatic disease, the expected effect is:
- Increased therapeutic effect due to reduced metabolism
- Reduced therapeutic effect due to impaired prodrug activation (Correct answer)
- No change in efficacy since prodrug and active form are equivalent
- Increased toxicity from prodrug accumulation only
Correct answer: Reduced therapeutic effect due to impaired prodrug activation
Hepatic disease impairs conversion of prodrug to active metabolite, reducing therapeutic efficacy; the prodrug itself has little or no pharmacological activity.
Question 6: Which pharmacokinetic process is described by the equation: Rate of elimination = Vmax × C / (Km + C)?
- First-order linear elimination
- Michaelis-Menten (saturable) elimination (Correct answer)
- Zero-order renal secretion
- Passive glomerular filtration
Correct answer: Michaelis-Menten (saturable) elimination
The Michaelis-Menten equation describes saturable enzyme kinetics where Vmax is maximum elimination rate and Km is the concentration at half-maximal rate.
Question 7: Therapeutic drug monitoring (TDM) is MOST useful for drugs with which characteristics?
- Wide therapeutic index and predictable pharmacokinetics
- Narrow therapeutic index and high interpatient pharmacokinetic variability (Correct answer)
- Short half-life and complete renal elimination
- High bioavailability and no protein binding
Correct answer: Narrow therapeutic index and high interpatient pharmacokinetic variability
TDM is most valuable when the margin between efficacy and toxicity is small AND when inter-individual variability makes dose-response prediction unreliable without measured levels.
FPGEE Pharmacokinetics 5
A patient on warfarin (narrow therapeutic index, highly albumin-bound) is started on a second drug that also binds albumin avidly.
What is the initial expected pharmacokinetic consequence?