Toxicokinetics and Metabolism Flashcards
6 cards from real ABT practice questions. Tap to flip, then mark Knew It or Still Learning — missed cards come back until you master them.
Read the first 6 Toxicokinetics and Metabolism flashcards as text
Physiologically based pharmacokinetic (PBPK) modeling is most useful in toxicology for:
Answer: Extrapolating toxicokinetic data across species, routes, and dose levels
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.
CYP2D6 'poor metabolizers' (PMs) are at increased risk for toxicity from drugs that are CYP2D6 substrates because they:
Answer: Lack functional CYP2D6 and cannot metabolize substrates to inactive metabolites
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.
The area under the concentration-time curve (AUC) is directly proportional to which pharmacokinetic parameter?
Answer: Bioavailability / clearance (F/CL)
AUC = F × Dose / CL; for a given dose and bioavailability, AUC is inversely proportional to clearance and directly represents total systemic exposure.
Which process explains enterohepatic recirculation and its effect on drug half-life?
Answer: Drugs are reabsorbed from intestinal secretions after biliary excretion, extending their half-life
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.
The Michaelis-Menten equation describes enzyme-mediated metabolism; at concentrations far below Km, metabolism approaches:
Answer: First-order kinetics (rate proportional to concentration)
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.
CYP1A1 induction by polycyclic aromatic hydrocarbons (PAHs) increases risk of carcinogenicity because:
Answer: CYP1A1 converts PAH procarcinogens to reactive diol-epoxides that form DNA adducts
CYP1A1 (induced by PAH-AhR signaling) converts PAH procarcinogens like benzo[a]pyrene to reactive diol-epoxide metabolites (BPDE) that form covalent DNA adducts leading to mutagenesis.