Kinetics question for you smarties

[393656]

---

Members don't see this ad.

Hey all-I am coming to the close of my Psychiatry residency and think one of the coolest things about my field is the great pharmacology involved. I really have a ton of respect for any pharm peeps as the so many doctors do not know absolutely any pharm I tell ya.

Anyway-I have been trying to figure something out and its just beyond my thinking so needed the experts-you guys. Ill give you the example I have been thinking about.

Remeron has a high affinity/low Ki for H1 receptors. Obviously so does benadryl. I do not have the Ki's handy but lets assume for this that remeron has a Ki-.4uM and benadryl also has a Ki of .4 uM (any number would do I guess)
Now my question is how do you factor in the mg doses of each to compare one dose's overally effect to another. For example if you take Remeron 15mg (a common dose) and benadryl 50mg, even though they have the same Ki (in this example) how do you factor in the dose??

I tried to convert the mg to moles and that is as far as I got, did not know where to go. The point is often you see values in psychiatry for many receptors that dictate side-effects primarly but its hard to compare between other drugs by Ki since I do not know how to account for a dose comparison.

Thanks guys I will absolutely kneel and praise anyone who can help me out-this has been bugging me for awhile! thanks!

 

[rjk]

comparing 2 drugs like that is very difficult due to the varying PK parameters.
You've got differing Vds, and you've got to worry about the BBB.

You're right that you would have to break it down to the molar concentrations, but the partitioning makes it very tough to predict. without knowing the concentrations that occur in the brain at steady state, you'd have a fairly difficult time comparing the affinities.

 

[npage148]

Without unbound concentrations at the site of the receptor you can't do much. You could look at microdialysis studies to get some idea of unbound brain concentrations and its permeability/transport across the BBB.

 

[cashmonyz]

good research question for medicinal chem/pharmaceutic pharmacists