Which statement correctly defines the 'therapeutic index' (TI) and its clinical relevance?
- A TI = ED50 / LD50; a high TI indicates a narrow margin between effective and lethal doses
- B TI = LD50 / ED50; a high TI indicates a wide margin of safety between effective and lethal doses, and a low TI indicates a drug requiring careful monitoring (e.g., digoxin, lithium, aminoglycosides) ✓
- C TI = EC50 / IC50; a high TI means the drug is less effective
- D TI = Cmax / Cmin; it represents the peak-to-trough ratio during dosing interval
Correct answer: B. TI = LD50 / ED50; a high TI indicates a wide margin of safety between effective and lethal doses, and a low TI indicates a drug requiring careful monitoring (e.g., digoxin, lithium, aminoglycosides)
Explanation
The therapeutic index (TI) = LD50 / ED50 in animal studies (or TD50/ED50 using toxic dose). A high TI means there is a large difference between the effective and lethal/toxic dose—the drug is relatively safe (e.g., penicillins, TI very high). Drugs with low TI (digoxin, lithium, warfarin, aminoglycosides, phenytoin, methotrexate) have a narrow margin between therapeutic and toxic concentrations and require therapeutic drug monitoring (TDM). The Cmax/Cmin ratio describes dosing interval pharmacodynamics, not TI.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.