Define therapeutic index and explain why a narrow therapeutic index necessitates careful dosing and monitoring.

• A. TI = effective dose / toxic dose; narrow TI means large dosing margins.
• B. TI measures time to onset of action.
• C. TI = toxic dose / effective dose; narrow TI means small changes can cause toxicity or loss of efficacy; requires close monitoring.
• D. TI is the ratio of peak to trough levels.

Answer: (C)

The main idea here is the safety margin between the dose that provides the desired effect and the dose that causes toxicity. Therapeutic index is defined as the ratio of the toxic dose to the effective dose (TD50/ED50). A narrow therapeutic index means those two doses are close together, so small changes in dose, absorption, distribution, metabolism, or excretion, or in drug interactions or organ function, can push the level from therapeutic to toxic—or from subtherapeutic to therapeutic. That’s why drugs with a narrow TI require careful, individualized dosing and close monitoring, often with therapeutic drug monitoring to keep blood levels within a target range.

In practice, this is why clinicians titrate doses slowly, watch for signs of toxicity, adjust for renal/hepatic function and interactions, and may measure serum drug concentrations when available. Conversely, a wide therapeutic index means a larger safety margin and less intensive monitoring.

The other statements don’t fit because therapeutic index is not about time to onset, and it’s not simply a peak-to-trough ratio; it specifically reflects the ratio between toxic and effective doses, indicating safety margins.