Direct numerical simulation: Difference between revisions

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The term '''half maximal effective concentration''' ('''EC<sub>50</sub>''') refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.<ref>[http://www.graphpad.com/curvefit/introduction89.htm Introducing dose response curves], Graphpad Software</ref>  It is commonly used as a measure of drug's potency.
 
The EC<sub>50</sub> of a ''graded'' [[dose response curve]] therefore represents the concentration of a compound where 50% of its maximal effect is observed.<ref>[http://www.biochem.northwestern.edu/holmgren/Glossary/Definitions/Def-E/EC50.html EC50 definition]</ref>
The EC<sub>50</sub> of a ''quantal'' dose response curve represents the concentration of a compound where 50% of the population exhibit a response,<ref>[http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190116.htm definition of EC<sub>50</sub> for quantal dose response curve]</ref> after a specified exposure duration.
 
It is also related to [[IC50|IC<sub>50</sub>]] which is a measure of a compound's inhibition (50% inhibition). For competition binding assays and functional antagonist assays [[IC50|IC<sub>50</sub>]] is the most common summary measure of the dose-response curve.  For agonist/stimulator assays the most common summary measure is the EC<sub>50</sub>.<ref>[http://www.ncgc.nih.gov/guidance/section3.html Assay Operations for SAR Support] NIH Chemical Genomics Center</ref>
 
A small changes in [[ligand]] concentration typically result in rapid changes in response in the biological system, following a [[Sigmoid function|sigmoid]]al function.The [[inflection point]] at which the increase in response with increasing ligand concentration begins to slow is the EC<sub>50</sub>. Which can be mathematically determined by derivation of the best-fit line. While relying on a graph for estimation is more convenient, this typical method yields less accurate results and less precise.<ref>[http://www.ncgc.nih.gov/guidance/section3.html Assay Operations for SAR Support] NIH Chemical Genomics Center</ref>
 
== Equation ==
Many different equations can be used to derive an EC<sub>50</sub>. One possible function is:
 
<math>Y = Bottom + \frac{Top - Bottom}{1 + (\frac{X}{EC_{50}})^{\mathrm{-Hill coefficient}} }</math>
 
where Y is the observed value, Bottom is the lowest observed value, Top is the highest observed value, and the [[Hill coefficient]] gives the largest absolute value of the slope of the curve.<ref>[http://www.sigmaplot.com/products/sigmaplot/Standard_Curves_Analysis.pdf EC50 equation] - see page 5</ref>
 
== Limitations ==
 
The effects of a stressor or drug generally depend on the exposure time. Therefore, the EC<sub>50</sub> (and similar statistics) will be a function of exposure time. The exact shape of this time function will depend upon the stressor (e.g., the specific toxicant), its mechanism of action, the organism exposed, etc. This time dependency hampers the comparison of [[Potency (pharmacology)|potency]] or [[toxicity]] between compounds and between different organisms.
 
== See also ==
* [[Measures of pollutant concentration]]
* [[Dose-response relationship]]
* [[Certain safety factor]]
* [[IC50|IC<sub>50</sub>]] (half maximal inhibitory concentration)
* [[LD50|LD<sub>50</sub>]] (median lethal dose)
* [[Therapeutic index]]
 
== References ==
<references/>
 
== External links ==
* [http://www.changbioscience.com/stat/ec50.html Online IC50 Calculator]
* [http://www.unmc.edu/Pharmacology/receptortutorial/competition/IC50.htm Determination of IC<sub>50</sub> values]
* [http://pharmrev.aspetjournals.org/cgi/content/full/55/4/597 Neubig et al. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev. 2003 Dec;55(4):597-606.]
 
{{DEFAULTSORT:Ec50}}
[[Category:Pharmacology]]
[[Category:Toxicology]]

Revision as of 21:57, 14 December 2013

The term half maximal effective concentration (EC50) refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.[1] It is commonly used as a measure of drug's potency.

The EC50 of a graded dose response curve therefore represents the concentration of a compound where 50% of its maximal effect is observed.[2] The EC50 of a quantal dose response curve represents the concentration of a compound where 50% of the population exhibit a response,[3] after a specified exposure duration.

It is also related to IC50 which is a measure of a compound's inhibition (50% inhibition). For competition binding assays and functional antagonist assays IC50 is the most common summary measure of the dose-response curve. For agonist/stimulator assays the most common summary measure is the EC50.[4]

A small changes in ligand concentration typically result in rapid changes in response in the biological system, following a sigmoidal function.The inflection point at which the increase in response with increasing ligand concentration begins to slow is the EC50. Which can be mathematically determined by derivation of the best-fit line. While relying on a graph for estimation is more convenient, this typical method yields less accurate results and less precise.[5]

Equation

Many different equations can be used to derive an EC50. One possible function is:

Y=Bottom+TopBottom1+(XEC50)Hillcoefficient

where Y is the observed value, Bottom is the lowest observed value, Top is the highest observed value, and the Hill coefficient gives the largest absolute value of the slope of the curve.[6]

Limitations

The effects of a stressor or drug generally depend on the exposure time. Therefore, the EC50 (and similar statistics) will be a function of exposure time. The exact shape of this time function will depend upon the stressor (e.g., the specific toxicant), its mechanism of action, the organism exposed, etc. This time dependency hampers the comparison of potency or toxicity between compounds and between different organisms.

See also

References

External links