THERAPEUTIC INDEX AND THERAPEUTIC WINDOW

 

INTRODUCTION:  Administering a dose of the drug that produces an optimum therapeutic response for each individual patient is only one component of effective pharmacotherapy. Medical practitioners must also be able to predict whether the dose is safe for the patient and this is one other thing that is fully tested during clinical trials.  Frequency distribution curves can also be used to represent the safety of a drug. For example, the median lethal dose (LD₅₀) is often determined in preclinical trials, as part of the drug development process. The LD₅₀ is the dose of drug that will be lethal in 50% of the investigation group of animals. As with ED₅₀, a group of animals will exhibit considerable variability in lethal dose; what may be a nontoxic dose for one animal may be lethal for another.

DETERMINATION OF THERAPEUTIC INDEX:  To examine the safety of a particular drug, the LD₅₀ can be compared with the ED_50. For example, 10 mg of drug X is the average effective dose, and 40 mg is the average lethal dose. The ED₅₀ and LD₅₀ can then be used to calculate an important value in pharmacology, a drug’s therapeutic index, which is the ratio of a drug’s LD₅₀ to its ED₅₀.  

THERAPEUTIC WINDOWS:  Now that we have looked at therapeutic index as a ration, therapeutic window on the other side, is a range between the drug that can cause a desired effect in 50% also known as Effective dose 50 (ED50) of the investigational animals to the drug dose that can cause toxicity in 50% of the investigational animals also known as Toxic dose 50 (TD50).

INTERPRETATION OF THERAPEUTIC INDEX:  The larger the difference between the two doses, the greater the therapeutic index. In the example above, the therapeutic index is 4 (40 mg ÷ 10 mg). Essentially, this means that it would take an error in magnitude of approximately 4 times the average dose to be lethal to a patient. Thus, the therapeutic index is a measure of a drug’s safety margin.  The higher the value, the safer the medication.

MEDICAL IMPLICATIONS OF THERAPEUTIC INDEX:  The therapeutic index offers the medical personnel practical information on the safety of a drug and a means to compare one drug with another. Because the LD₅₀ cannot be experimentally determined in humans, the median toxicity dose (TD₅₀) is a more practical value in a clinical setting. The TD₅₀ is the dose that will produce a given toxicity in 50% of a group of patients. The TD50 value may be extrapolated from animal data or based on adverse effects recorded in patient clinical trials.

 

RELATED;

1. PHASES OF CLINICAL TRIALS

2. DRUG DISCOVERY AND DEVELOPMENT

3. RANDOMISATION

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES