Ki and dose relationship

[Nucleus]

Hi,

is there a way to calculate the effective dose when i have the Ki value for its receptor binding? Lets say drug A bind to D2 with Ki of 200. What would be the minimal dose for reaching antipychotic effetc? I know there are tons of other factors that may influence that, but i dont want a correct scientific calculation - just a orientation.

 

[S.J.B.]

It's completely impossible. Look into the term "ADME" for some of the reasons why it is impossible.

 

[sekio]

there is a table of typical drug concentrations in serum availiable in Clarke's Analysis of Drugs and Poisons that helps, so if you know e.g. a "typical" dose of some drug reaches 1-3 uM in serum then in OD maybe we will see 20-60 uM... and you can then compare with known Ki/IC50... if said drug hits "target A" at 0.8uM and "target B" at 15uM then we can assume "target A" will be bound vy the drug in almost all cases, and "target B" will only be bound in OD.

but this does not take into effect the fact that a drug may be concentrated in certain places, so serum levels will not neccesarily reflect its presence in e.g. fat, muscle, eye, bile, sweat, tears, semen, milk, CSF...

 

[Hodor]

Hi,

is there a way to calculate the effective dose when i have the Ki value for its receptor binding? Lets say drug A bind to D2 with Ki of 200. What would be the minimal dose for reaching antipychotic effetc? I know there are tons of other factors that may influence that, but i dont want a correct scientific calculation - just a orientation.

Look at the binding affinities for sertraline (Zoloft). If you compare its affinity for the dopamine transporter to that of a typical NDRI like methylphenidate or cocaine, you'd think that a single 50 mg Zoloft pill should provide euphoric stimulation... that is, if it didn't instantly give you serotonin syndrome because of the drug's insanely high affinity for the serotonin transporter.

Yet in reality, a normal therapeutic dose of sertaline (100 mg) is an order of magnitude greater than the therapeutic dose for escitalopram (10 mg) and there is no noticeable dopaminergic stimulation, since 98-99% of a zoloft dose ends up uselessly sticking to plasma proteins instead of plugging your serotonin transporters like it's supposed to.

So yes, trying to calculate an active dose from Ki values alone is a rather imprecise affair.

 

[negrogesic]

No but you can often get a sense.