ABT Toxicokinetics and Metabolism 2

Question 1

Physiologically based pharmacokinetic (PBPK) modeling is most useful in toxicology for:

Accepted Answer

Extrapolating toxicokinetic data across species, routes, and dose levels

Answer

PBPK models use physiological parameters (organ volumes, blood flows) and chemical-specific parameters to extrapolate internal dose across species (animal to human), routes, and dose levels in risk assessment.

Question 2

CYP2D6 'poor metabolizers' (PMs) are at increased risk for toxicity from drugs that are CYP2D6 substrates because they:

Accepted Answer

Lack functional CYP2D6 and cannot metabolize substrates to inactive metabolites

Answer

CYP2D6 poor metabolizers (5–10% of Caucasians) carry loss-of-function alleles and cannot efficiently metabolize substrates, leading to drug accumulation and increased toxicity risk.

Question 3

The area under the concentration-time curve (AUC) is directly proportional to which pharmacokinetic parameter?

Accepted Answer

Bioavailability / clearance (F/CL)

Answer

AUC = F × Dose / CL; for a given dose and bioavailability, AUC is inversely proportional to clearance and directly represents total systemic exposure.

Question 4

Which process explains enterohepatic recirculation and its effect on drug half-life?

Accepted Answer

Drugs are reabsorbed from intestinal secretions after biliary excretion, extending their half-life

Answer

Enterohepatic recirculation occurs when drugs excreted in bile into the intestine are deconjugated by gut bacteria and reabsorbed, creating a drug reservoir that extends apparent half-life.

Question 5

The Michaelis-Menten equation describes enzyme-mediated metabolism; at concentrations far below Km, metabolism approaches:

Accepted Answer

First-order kinetics (rate proportional to concentration)

Answer

When substrate concentration is far below Km (the Michaelis constant), the enzyme is far from saturated and the reaction velocity is approximately proportional to substrate concentration — i.e., pseudo-first-order kinetics.

ABT - American Board of Toxicology Practice Test

ABT - American Board of Toxicology Practice Test

ABT Toxicokinetics and Metabolism 2