Which of the following statements regarding drug half-life is correct?

Question

BlackTom AI · Accepted Answer

Half-life (t1/2) is related to volume of distribution (Vd) and clearance (CL) by the fundamental equation:
t1/2 = 0.693 × Vd / CL.

1) Relevant concepts
- Half-life (t1/2): time for plasma concentration to fall by 50% during first-order elimination.
- Clearance (CL): volume of plasma completely cleared of drug per unit time.
- Volume of distribution (Vd): apparent volume that relates amount of drug in body to plasma concentration.
- Elimination rate constant (ke): ke = CL / Vd, and t1/2 = 0.693 / ke.

2) Step-by-step reasoning and intermediate steps
Start from ke = CL / Vd.
t1/2 = 0.693 / ke
Substitute ke:
t1/2 = 0.693 / (CL / Vd) = 0.693 × Vd / CL.
Thus t1/2 is directly proportional to Vd and inversely proportional to CL. Also, since ke = CL/Vd, increasing CL raises ke and therefore shortens t1/2 (because t1/2 = 0.693/ke).

3) Why option d is correct
Option d: "Half-life decreases as clearance increases." From t1/2 = 0.693 × Vd / CL, if CL increases (Vd constant), the denominator increases and t1/2 decreases. Equivalently, increased CL → increased ke → decreased t1/2. This directly matches the mathematical relationship, so d is correct.

4) Why the other options are incorrect
- a: "Half-life is independent of Vd" is false because t1/2 ∝ Vd; larger Vd → longer t1/2 if CL unchanged.
- b: "Half-life decreases as elimination rate constant decreases" is the opposite of reality. Since t1/2 = 0.693 / ke, if ke decreases, t1/2 increases.
- c: "Half-life increases following intravenous administration" is misleading; route of administration (IV vs oral) does not change the intrinsic elimination half-life once drug is in systemic circulation (assuming linear kinetics). IV may change early distribution profile, but not the elimination half-life determined by Vd and CL.

Conclusion: Based on t1/2 = 0.693 × Vd / CL and ke = CL/Vd, the correct answer is (d) Half-life decreases as clearance increases, which matches the provided answer.

Which of the following statements regarding drug half-life is correct?单项选择题

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