U01.05.012 Therapeutic index

The therapeutic index (TI) is a critical measure for assessing the safety of a drug. It provides an understanding of the margin between the dose that is effective in treating a disease and the dose that can be toxic to the body.

Formula for Therapeutic Index

Therapeutic Index (TI) = TD₅₀ / ED₅₀

Where:

TD₅₀ = Median Toxic Dose
ED₅₀ = Median Effective Dose

Key Concepts

Safer Drugs: Drugs with a higher therapeutic index are considered safer because the effective dose (ED₅₀) is much lower than the toxic dose (TD₅₀), providing a broader margin of safety.
Drugs Requiring Monitoring: Drugs with a lower TI have a smaller margin between therapeutic and toxic doses, making them more dangerous and often requiring close monitoring. Common examples include:
- Warfarin
- Theophylline
- Digoxin
- Antiepileptic drugs
- Lithium
LD₅₀ (Lethal Median Dose): In animal studies, the LD₅₀ (lethal dose) is used in place of TD₅₀ to estimate the lethal dose that kills 50% of the population.

Therapeutic Window

The therapeutic window refers to the dosage range within which a drug can be administered safely and effectively. It is the range between the ED₅₀ and TD₅₀ where most patients will experience therapeutic effects without severe toxicities.

Graphical Representation of Therapeutic Index

Drug Concentration (%)	Response (Effect)	Toxicity (%)
0%	No effect	No toxicity
50%	ED₅₀ (Effective Dose)	Threshold for toxicity begins
100%	Full therapeutic effect	Toxicity increases
Log (Drug Concentration)

Note: As the drug concentration increases (log scale), therapeutic effects increase, but so does the risk of toxicity once the therapeutic index is surpassed.

Points to Remember

A higher TI means a safer drug.
Drugs with a low TI (e.g., Warfarin, Theophylline, Lithium) require close monitoring.
The therapeutic window is the range where a drug is both effective and safe.
LD₅₀ is used in animal studies and represents the dose that kills 50% of subjects.

USMLE Step 1 Review Series

Curriculum