Therapeutic Index and Therapeutic Range - Pharmacology

Drugs have a pharmaceutical response as long as the dose remains within the drug’s margin of safety. Some drugs have a broad margin of safety. This means that a patient can be given a wide range of dose levels without experiencing a toxic effect. Other drugs have a narrow margin of safety where a slightest change in the dose can result in an undesirable adverse side effect. The drug’s Therapeutic Index (TI) identifies the margin of safety of the drug and is a ratio between the therapeutic dose in 50% of persons/animals and the lethal dose in 50% of animals. The therapeutic dose is notated as ED50 and the lethal dose in animals is noted as LD50. The closer that the ratio is to 1, the greater the danger of toxicity. TI = LD50/ED50

Drugs that have a low TI are said to have a narrow margin of safety. These drugs require that levels in the plasma be monitored and adjustments are made to the dosage in order to prevent a toxic effect from occurring.

The plasma drug levels must be within the therapeutic range, which is also known as the therapeutic window. The therapeutic range is between the minimum effective concentration (MEC) for obtaining the desired pharmaceutical response and the minimum toxic concentration (MTC). MEC is achieved by administering a loading dose, which is a large initial dose given to achieve a rapid plasma MEC.

PEAK AND TROUGH LEVELS

The plasma concentration of a drug must be monitored for drugs that have a narrow margin of safety or low therapeutic index. The concentration is measured at two points. These are the peak drug level and the trough level.

The peak drug level is the highest plasma concentration at a specific time. Peak levels indicate the rate a drug is absorbed in the body and is affected by the route used to administer the drug. Drugs administered intravenously have a fast peak drug level while a drug taken orally has a slow peak drug level because the drugs needs time to be absorbed and distributed. Blood samples are drawn at peak times based on the route used to administer the drug. This is usually 1/2 to 1 hr after drug administration.

The trough level is the lowest plasma concentration of the drug and measures the rate at which the drug is eliminated. Blood should be drawn immediately before the next dose is given regardless of the route used to administer the drug.


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