Which statement correctly describes the concept of therapeutic index (TI) and its clinical implication?
- A TI = ED50/LD50; drugs with TI > 1 are safe to use clinically
- B TI = Cmax/MIC; drugs with TI > 10 are considered concentration-dependent killers
- C TI = LD50/ED50; a drug with a narrow TI requires careful dose titration and monitoring because toxic and therapeutic doses overlap ✓
- D TI = AUC therapeutic/AUC toxic; it is independent of the dose-response relationship
Correct answer: C. TI = LD50/ED50; a drug with a narrow TI requires careful dose titration and monitoring because toxic and therapeutic doses overlap
Explanation
The therapeutic index (TI) = LD50/ED50 (or the analogous TD50/ED50 in humans). A higher TI indicates a wider safety margin. Drugs with a narrow TI — such as warfarin, digoxin, lithium, aminoglycosides, phenytoin — have toxic doses close to therapeutic doses, requiring plasma level monitoring and careful titration. The TI is derived from graded or quantal dose-response curves, not from PK parameters like AUC or Cmax.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.