Interpreting values relative to P-Glyoprotein inhibition/induction?

[JohnBoy2000]

Basically - Venlafaxine induces p-glycoprotein, such to reduce indinavir levels by 30%

I attempting to determine Mianserin based p-glycoprotein inhibition or induction.

So - I haven't a notion, outside of reading something to the effect of values close to 1 mean no implication via P-GP.

But maybe ya'll know for sure?

For MIANSERIN:

​

PROPERTY	VALUE	PROBABILITY

​

P-glycoprotein substrate	Substrate	0.8676
P-glycoprotein inhibitor I	Inhibitor	0.8198
P-glycoprotein inhibitor II	Non-inhibitor	0.9067

So - can anyone tell me - what that means?

I get it's saying, to some degree inhibitor, to some degree a substrate - but given the values, are they significant?​

 

[JohnBoy2000]

Comparing that with ​

Mirtazapine

- which is clinically deemed a non-substrate or inhibitor of P-GP:

​

P-glycoprotein substrate	Substrate	0.8462
P-glycoprotein inhibitor I	Inhibitor	0.6148
P-glycoprotein inhibitor II	Non-inhibitor	0.8975

In turn compared with Atomoxetine - which is noted in literature as a non P-GP inhibitor/substrate:​

P-glycoprotein substrate	Substrate	0.6133
P-glycoprotein inhibitor I	Inhibitor	0.7771
P-glycoprotein inhibitor II	Non-inhibitor	0.8003

 

[sekio]

These are not affinities or anything, it looks like probability weightings from the output of a neural network.

The closer the value is to 1, the more likely that the drug will act in the specified way, so e.g. atomoxetine is predicted as 61% probability of being a PGP substrate, 77% chance it inhibits PGP-1, and 80% chance it is a non-inbhibitor of PGP-2.

I don't think these are accurate numbers.

 

[JohnBoy2000]

I've got one more critical question - that may or may not be possible to even answer.


37.5 mg venlafaxine - used in conjunction with Atomoxetine - dosed night time - induced night time activation.

Without Atomoxetine - I can take it at night time and sleep fine.

If I replaced venlafaxine with Citalopram or Lexapro or Sertraline - could I still expect that night time activation - or is it attributable to the minimal noradrenergic effect of Venlafaxine?

Or - is that night time activation attributable to the serotonergic effect boosting the NA effect of Atomoxetine, via common post synaptic effectors? Thus - any of the other SSRI's would basically yield a similar effect?

 

[JohnBoy2000]

I've been having trouble pulling up a relevant paper on the noradrenergic implications of Venlafaxine according to dose; 75, 150, 225 - etc - in regards to being supposedly a serotonergic exclusively up to 150 mg.

If anyone can put their hands on a paper to that effect??