Can anyone explain about the minimum dose required to see any effect based on EC50 or IC50? I mean, if some drug has IC50 (24 pM) then what minimum concentration of drug would be best in animal (in vivo) to see the inhibitory effects.
You need the molecular weight of the compound you want to test and then you can use the calculator at the link attached. Sorry to be so short but the calculator works much better that any explanation I may provide. Then you can find the concentrations to be tested corresponding to your IC50 and lower ICs..
The half maximal inhibitory concentration (IC50) is a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function.
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. The values are typically expressed as molar concentration
It is commonly used as a measure of antagonist drug potency in pharmacological research. 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.
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 can be used to compare the potency of two antagonists.
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] Sometimes it is also expressed as pEC50 = - LOG(EC50) (with EC50 in M/l).
A small change 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.
When looking to estimate a dose to administer in animals you need to consider some points. You want the unbound (free) concentration at the site of action (target) to be in the range for which effect is expected (from in vitro assay: IC50 or EC50 or better IC90/EC90).
If you do not have information on this (as is usual), you can assume that it will be the same as the unbound concentration in plasma (Cup). You need then to estimate the corresponding total plasma concentration (Cp): Cp=Cup/fup; with fup the free fraction in plasma.
The dose is then the dose that provides such plasma concentrations, you can estimate it from preliminary pharmacokinetic (PK) data.
You may want to consider a possible time delay in equilibration between plasma and the site of action (depending on tissue). This may lead to a later Tmax and lower Cmax. If your in vivo measure is a direct PD measurement of target modulation you should take measurements at different times after administration. If your measure is for efficacy after chronic administration, you can aim at a dose that provides an average concentration (Cav=AUC/dosing interval) corresponding to the concentration calculated above.