Inpharmacology,aneffective dose(ED) oreffective concentration(EC) is thedoseorconcentrationof adrugthat produces a biological response.[1][2]The term "effective dose" is used when measurements are takenin vivo,while "effective concentration" is used when the measurements are takenin vitro.[3]
It has been statedthat any substance can be toxic at a high enough dose. This concept was exemplified in 2007 when a California woman died ofwater intoxicationina 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 predeterminedtherapeutic windowof the drug.
The importance of determining the therapeutic range of a drug cannot be overstated. This is generally defined by the range between theminimum effective dose(MED) and themaximum 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
editThemedian effective doseis 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 TD50and LD50respectively. Ideally, the effective dose would be substantially less than either the toxic or lethal dose for a drug to be therapeutically relevant.
ED95
editTheED95is the dose required to achieve the desired effect in 95% of the population.
In anaesthesia, the term ED95is 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 ED50for 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
editReferences
edit- ^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.ISSN0277-6715.PMID7569511.
- ^Street, Farnam (2014-02-13)."The Minimum Effective Dose: Why Less is More".Farnam Street.Retrieved2023-05-23.
- ^Rang HP, Dale MM, Flower RJ, Henderson G (2015-01-21).Rang and Dale's pharmacology(Eighth ed.). United Kingdom: Elsevier Churchill Livingstone.ISBN9780702053627.OCLC903083639.
- ^"Woman Dies After Water-drinking Contest".NBC. Associated Press.
- ^abcLiu Jp (2010). "Minimum Effective Dose". In Chow SC (ed.).Encyclopedia of Biopharmaceutical Statistics.Taylor & Francis.doi:10.1081/E-EBS3.ISBN978-1-4398-2246-3.
- ^IUPAC,Compendium of Chemical Terminology,2nd ed. (the "Gold Book" ) (1997). Online corrected version: (2006–) "median effective dose, ED50".doi:10.1351/goldbook.M03808
- ^Miller R, Eriksson L, Fleisher L, Wiener-Kronish J, Young W (May 2009).Miller's Anesthesia(7th ed.). Churchill Livingstone. pp.500–504.ISBN978-1-4557-0876-5.