Effective dose (pharmacology)

"ED-50" redirects here. For the geodetic datum ED50, see ED50.

An effective dose (ED) in pharmacology is the dose or amount of drug that produces a therapeutic response or desired effect in some fraction of the subjects taking it.

It has been stated that any substance can be toxic at a high enough dose. This concept was exemplified in 2007 when a California woman died of water intoxication in a contest sanctioned by a radio station.[1] The line between efficacy and toxicity is dependent upon the particular patient, although the dose administered by a physician should fall into the predetermined therapeutic window of the drug.

The importance of determining the therapeutic range of a drug cannot be overstated. This is generally defined by the range between the minimum effective dose (MED) and the maximum tolerated dose (MTD). The MED is defined as the lowest dose level of a pharmaceutical product that provides a clinically significant response in average efficacy, which is also statistically significantly superior to the response provided by the placebo.[2] Similarly, the MTD is the highest possible but still tolerable dose level with respect to a pre-specified clinical limiting toxicity.[2] In general, these limits refer to the average patient population. For instances in which there is a large discrepancy between the MED and MTD, it is stated that the drug has a large therapeutic window. Conversely, if the range is relatively small, or if the MTD is less than the MED, then the pharmaceutical product will have little to no practical value.[2]

ED50

The "median effective dose" is the dose that produces a quantal effect (all or nothing) in 50% of the population that takes it (median referring to the 50% population base). It is also sometimes abbreviated as the ED50, meaning "effective dose, for 50% of people receiving the drug". The ED50 is commonly used as a measure of the reasonable expectancy of a drug effect, but does not necessarily represent the dose that a clinician might use. This depends on the need for the effect, and also the toxicity. The toxicity and even the lethality of a drug can be quantified by the TD50 and LD50 respectively. Ideally, the effective dose would be substantially less than either the toxic or lethal dose for a drug to be therapeutically relevant.


ED95

The ED95 is the dose required for desired effect in 95% of the population exposed to it.

In Anaesthesia Pharmacology, the term ED95 is used in a different context and thus, commonly misunderstood to correspond to the median dose required to achieve a quantal effect in 95% of the population. This is erroneous.

Its correct use and definition is with reference to non-depolarising neuromuscular blocking agents. ED95 in this context is the median dose required to achieve a 95% reduction in maximal twitch response from baseline, in 50% of the population. The single twitch response occurs when applying a square wave "supra-maximal" current, using a nerve stimulator, to the ulnar nerve and measuring twitch of the adductor pollicus.

Thus, the more accurate use of the term in this regard would be "ED5095. Notwithstanding, usage of the term "ED95" has stuck in this context.

Alternative definition: ED95 (when referring to non depolarising muscle relaxants) is the ED50 from a cumulative log dose response curve where the quantum is a 95%reduction in twitch height

Notes

  1. ↑ "Woman Dies After Water-drinking Contest". NBC. Associated Press. Retrieved 7 May 2015.
  2. 1 2 3 Jen-pei, Liu (2010). Encyclopedia of Biopharmaceutical Statistics. Taylor & Francis. p. 1493. ISBN 978-1-4398-2246-3.

See also

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