Learning Objective
Understand how quantal dose-response curves are used to evaluate drug safety by comparing therapeutic and toxic effects, and calculate the therapeutic index (TI).
Toxicity and Therapeutic Index (TI)
TD50 (Median Toxic Dose):
The dose that produces toxic effects in 50% of the population.
ED50 (Median Effective Dose):
The dose that produces the desired effect in 50% of a population.
LD50 (Lethal Dose 50):
The dose that causes death in 50% of the population (used in animal studies).
Therapeutic Index (TI):
Ratio indicating the relative safety of a drug.
Purpose of TI:
- Measures the safety margin of a drug.
- Higher TI → safer drug; lower TI → narrow safety margin.
Relationship to D-R Curves:
- Quantal D-R curves can display both therapeutic and toxic effects.
- The separation between ED50 and TD50 on the curve reflects the window of safe dosing.
Limitations:
- TI is most reliable when toxicity is an extension of the drug’s pharmacologic effect.
- Does not predict idiosyncratic reactions or hypersensitivity.
Example Calculation
- ED50 = 2 mg
- TD50 = 10 mg
- Interpretation: The toxic dose is 5 times higher than the effective dose.
