ABT Toxicokinetics and Metabolism 1 — Questions and Answers
Question 1: Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation unchanged?
- Volume of distribution (Vd)
- Clearance (CL)
- Bioavailability (F) (Correct answer)
- Half-life (t½)
Correct answer: Bioavailability (F)
Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation unchanged, accounting for absorption and first-pass metabolism.
Question 2: Which cytochrome P450 enzyme is responsible for metabolizing the largest number of pharmaceutical drugs (approximately 30–40%)?
- CYP1A2
- CYP2C9
- CYP3A4 (Correct answer)
- CYP2D6
Correct answer: CYP3A4
CYP3A4 is the most abundant hepatic and intestinal CYP enzyme and metabolizes approximately 30–40% of clinically used drugs, making it a key site of drug-drug interactions.
Question 3: A chemical with a high volume of distribution (Vd > 10 L/kg) is most likely to be:
- Highly water-soluble and confined to plasma
- Extensively bound to plasma proteins
- Highly lipophilic and distributed into peripheral tissues (Correct answer)
- Rapidly excreted by the kidneys without tissue binding
Correct answer: Highly lipophilic and distributed into peripheral tissues
A high volume of distribution indicates the drug is extensively distributed into peripheral tissues (fat, muscle), suggesting high lipophilicity or strong tissue protein binding.
Question 4: First-order elimination kinetics means that:
- A constant amount of drug is eliminated per unit time regardless of concentration
- The rate of elimination is directly proportional to the drug concentration (Correct answer)
- Elimination rate increases exponentially with dose
- Half-life increases as dose increases
Correct answer: The rate of elimination is directly proportional to the drug concentration
In first-order kinetics, a constant fraction (not amount) of drug is eliminated per unit time; the rate of elimination is proportional to drug concentration, resulting in a constant half-life.
Question 5: The hepatic extraction ratio (ER) of a drug determines whether its clearance is sensitive to changes in:
- Renal blood flow for high-ER drugs
- Hepatic blood flow for high-ER drugs and protein binding for low-ER drugs (Correct answer)
- GI motility only
- Intestinal CYP expression for low-ER drugs only
Correct answer: Hepatic blood flow for high-ER drugs and protein binding for low-ER drugs
High extraction ratio (ER > 0.7) drugs have flow-limited clearance sensitive to hepatic blood flow, while low ER drugs (< 0.3) have capacity-limited clearance sensitive to enzyme activity and protein binding.
Question 6: Which phase II biotransformation reaction is most important for detoxifying reactive electrophilic metabolites via conjugation with a tripeptide?
- Glucuronidation (UGT)
- Sulfation (SULT)
- Glutathione conjugation (GST) (Correct answer)
- Acetylation (NAT)
Correct answer: Glutathione conjugation (GST)
Glutathione S-transferases (GSTs) conjugate reactive electrophilic metabolites with glutathione (γ-Glu-Cys-Gly), detoxifying them and preventing cellular damage.
ABT Toxicokinetics and Metabolism 1
Which pharmacokinetic parameter describes the fraction of an administered dose that reaches systemic circulation unchanged?