Effective dose (pharmacology)

Not to be confused with EC50 (half maximal effective concentration) or Average treatment effect.
"ED-50" redirects here. For the geodetic datum ED50, see ED50.

In pharmacology, an effective dose (ED) or effective concentration (EC) is the dose or concentration of a drug that produces a biological response.[1][2] The term "effective dose" is used when measurements are taken in vivo, while "effective concentration" is used when the measurements are taken in vitro.[3]

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.[4] 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.[5] Similarly, the MTD is the highest possible but still tolerable dose level with respect to a pre-specified clinical limiting toxicity.[5] In general, these limits refer to the average patient population. For instances in which there is a large difference 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.[5]

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).[6] It is also sometimes abbreviated as the ED50, meaning "effective dose for 50% of the population". 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 to achieve the desired effect in 95% of the population.

In anaesthesia, the term ED95 is also used when referring to the pharmacology of neuromuscular blocking drugs. In this context, it is the dose which will cause 95% depression of the height of a single muscle twitch, in half of the population. Put another way, it is the ED50 for 95% reduction in twitch height.[7] The single twitch response occurs when a nerve stimulator is used to stimulate the ulnar nerve, and the degree of twitch of the adductor pollicus muscle is measured. A more accurate nomenclature when used in this way would be "ED5095".

See also

References

  1. ^ Filloon, T. G. (May 1995). "Estimating the minimum therapeutically effective dose of a compound via regression modelling and percentile estimation". Statistics in Medicine. 14 (9–10): 925–932, discussion 933. doi:10.1002/sim.4780140911. ISSN 0277-6715. PMID 7569511.
  2. ^ Street, Farnam (2014-02-13). "The Minimum Effective Dose: Why Less is More". Farnam Street. Retrieved 2023-05-23.
  3. ^ Rang HP, Dale MM, Flower RJ, Henderson G (2015-01-21). Rang and Dale's pharmacology (Eighth ed.). United Kingdom: Elsevier Churchill Livingstone. ISBN 9780702053627. OCLC 903083639.
  4. ^ "Woman Dies After Water-drinking Contest". NBC. Associated Press.
  5. ^ a b c Liu Jp (2010). "Minimum Effective Dose". In Chow SC (ed.). Encyclopedia of Biopharmaceutical Statistics. Taylor & Francis. doi:10.1081/E-EBS3. ISBN 978-1-4398-2246-3.
  6. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "median effective dose, ED50". doi:10.1351/goldbook.M03808
  7. ^ Miller R, Eriksson L, Fleisher L, Wiener-Kronish J, Young W (May 2009). Miller's Anesthesia (7th ed.). Churchill Livingstone. pp. 500–504. ISBN 978-1-4557-0876-5.