IC50 versus EC50

• The IC50 represents the concentration of a drug that is required for 50% inhibition of viral replication in vitro (can be corrected for protein binding etc).

• The EC50 represents the plasma concentration/AUC required for obtaining 50% of the maximum effect in vivo.

• http://www.fda.gov/ohrms/dockets/ac/00/slides/3621s1d/tsld036.htm

• IC50

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  The half maximal inhibitory concentration (IC₅₀) is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. Often, the compound in question is a drug candidate. This quantitative measure indicates how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process (or component of a process, i.e. an enzyme, cell, cell receptor or microorganism) by half. In other words, it is the half maximal (50%) inhibitory concentration (IC) of a substance (50% IC, or IC₅₀). It is commonly used as a measure of antagonist drug potency in pharmacological research. Sometimes, it is also converted to the pIC₅₀ scale (-log IC₅₀), in which higher values indicate exponentially greater potency. According to the FDA, IC₅₀ represents the concentration of a drug that is required for 50% inhibition in vitro.^[1] It is comparable to an EC₅₀ for agonist drugs. EC₅₀ also represents the plasma concentration required for obtaining 50% of a maximum effect in vivo.^[1]

• [edit] Determination IC₅₀ of a drug

  [edit] Functional antagonist assay

  The IC₅₀ of a drug can be determined by constructing a dose-response curve and examining the effect of different concentrations of antagonist on reversing agonist activity. IC₅₀ values can be calculated for a given antagonist by determining the concentration needed to inhibit half of the maximum biological response of the agonist.^[2]

  IC₅₀ values are very dependent on conditions under which they are measured. In general, the higher the concentration of inhibitor, the more agonist activity will be lowered. IC₅₀ value increases as enzyme concentration increases. Furthermore depending on the type of inhibition other factors may influence IC₅₀ value; for ATP dependent enzymes IC₅₀ value has an interdependency with concentration of ATP, especially so if inhibition is all of it competitive. IC₅₀ values can be used to compare the potency of two antagonists.

  [edit] Competition binding assays

  In this type of assay, a single concentration of radioligand (usually an agonist) is used in every assay tube. The ligand is used at a low concentration, usually at or below its K_d value. The level of specific binding of the radioligand is then determined in the presence of a range of concentrations of other competing non-radioactive compounds (usually antagonists), in order to measure the potency with which they compete for the binding of the radioligand. Competition curves may also be computer-fitted to a logistic function as described under direct fit.

  In this situation the IC₅₀ is the concentration of competing ligand which displaces 50% of the specific binding of the radioligand. The IC₅₀ value is converted to an absolute inhibition constant Ki) using the Cheng-Prusoff equation (see Ki).^[3][2]

  [edit] IC₅₀ and affinity

  IC₅₀ is not a direct indicator of affinity although the two can be related at least for competitive agonists and antagonists by the Cheng-Prusoff eqtn.^[4]

  

  where Ki is the binding affinity of the inhibitor, IC₅₀ is the functional strength of the inhibitor, [S] is substrate concentration and km is the affinity of the substrate for the enzyme.Whereas the IC₅₀ value for a compound may vary between experiments depending on radioligand concentration, the K_i is an absolute value. K_i is the inhibition constant for a drug; the concentration of competing ligand in a competition assay which would occupy 50% of the receptors if no radioligand were present.^[3]

Half maximal effective concentration

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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 some specified exposure time.^[1] It is commonly used as a measure of drug potency and toxicity.

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].

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]

Concentration measures typically follow a Sigmoidal curve, increasing rapidly over a relatively small change in concentration. The point at which the effectiveness slows with increasing concentration is the IC₅₀. This can be determined mathematically by derivation of the best-fit line. However, it is more easily observed from a graph and estimated rather than through complex calculus equations^{[citation needed]}.

Equation

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

Y = Bottom + (Top - Bottom)/(1 + (X/EC₅₀)^{(Hill coefficient)})

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.

And an alternate form of the equation is:

Y = Bottom + (Top - Bottom)/(1+ 10^{((Log(EC₅₀)-X) * (Hill coefficient))})

[edit] 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, etcetera. This time dependency hampers the comparison of potency or toxicity between compounds and between different organisms.

 

LC50：半数致死浓度，引起受试对象50%个体死亡的药物浓度。
IC50：半数抑制浓度 ，一种药物能将细胞生长、病毒复制等抑制50%所需的浓度。
EC50：半数效应浓度，引起受试对象50%个体产生一种特定效应的药物剂量。

What is the difference between an IC50 and an EC50 and an ED50?   FAQ# 1332

The differences are just nomenclature, and not conceptual. "EC" means effective concentration, and is used for dose-response curves that go up hill. "IC" means inhibitory concentration, so is used for dose-response curves that go downhill, because the drug inhibits a response.  In both cases, "C" stands for concentration. In some experiments, you vary the administered dose, but don't know the effective concentration. In these cases, the midpoint is called the ED50.