Therapeutic index refers to a measurement of a drug's safety, calculated as the ratio between the median lethal dose (LD50) and the median effective dose (ED50). A higher therapeutic index indicates a drug is safer, with a wider margin between toxic and effective doses. Drugs with a low therapeutic index require close monitoring due to the narrow margin between their toxic and effective doses. A therapeutic index above 10 is generally considered good.

1. THERAPEUTIC INDEX
PHM 301

2. Therapeutic Index
• Therapeutic index (TI) refers to any of the several indices that are
used for measuring a drug’s safety.
– A safer drug has a higher therapeutic index
– A more dangerous drug has a lower therapeutic index
• may require regular monitoring of drug levels
• examples include:
– Warfarin
– Lithium
– Digoxin
– Phenytoin
– Gentamicin
– Amphotericin
– 5-fluoro-uracil
– Zidovudine
• It is generally considered that a drug has a good safety profile if its
TI exceeds the value of 10

4. Definition of terms
•
LD50 stands for median lethal dose, and ED50 stands for
median effective dose.
• LD50 refers to the dose that would produce a lethal effect in
50% of the population,
• whereas ED50 refers to the dose that will produce the
desired therapeutic effect in 50% of the population.
• TD50 refers to the minimum drug dose that would produce
a toxic effect in 50% of the population

6. TI CURVES

8. SIGNIFICANCE
• The larger value of TI indicates that there is a
wide margin between the toxic and effective
dose.
• Smaller value indicates that there is a narrow
margin between the effective and toxic dose.
• Drugs that have a low TI, even a small
increase in the dosage can produce toxic
effects. Additional care must be taken while
prescribing a drug with a narrow TI.

9. Limitations
• Initially, the ratio of the LD50 and ED50 was
determined through animal studies.
• It must be noted that the ratio measured by
animal studies might not be very accurate when it
comes to humans.
• Human subjects cannot be used for determining
a median lethal dose, for obvious reasons.
• Using animals for determining a lethal dose raises
ethical issues.