In preclinical evaluation, a new hypnotic shows an ED99 of 2 mg/kg and an LD1 of 200 mg/kg in animal studies. Which term correctly describes the value 100 obtained from these figures, and why is it preferred over LD50/ED50 for safety assessment?
- A Margin of safety, because it compares the extremes of the effective and lethal curves where overlap matters clinically ✓
- B Therapeutic index, because it uses median doses that are statistically stable
- C Standard safety margin, expressed as a percentage derived from ED50 alone
- D Certainty safety factor, defined as TD1 divided by ED99
Correct answer: A. Margin of safety, because it compares the extremes of the effective and lethal curves where overlap matters clinically
Explanation
The ratio LD1/ED99 defines the margin of safety. It is preferred because if the tails of the quantal dose-response curves for benefit and lethality overlap, some patients may die at fully effective doses even when the conventional therapeutic index LD50/ED50 looks reassuring. Median-based indices ignore this tail overlap. The certainty safety factor uses TD1/ED99 for toxic rather than lethal endpoints, so option D names a related but different measure.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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Written and medically reviewed by the StethoPrep medical team.