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:

​

[TABLE="class: table table-sm responsive-table, width: 0"]
[TR]
[TH]PROPERTY[/TH]
[TH]VALUE[/TH]
[TH]PROBABILITY[/TH]
[/TR]
[/TABLE]

​

[TABLE="class: table table-sm responsive-table, width: 0"]
[TR]
[TD]P-glycoprotein substrate[/TD]
[TD]Substrate[/TD]
[TD]0.8676[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor I[/TD]
[TD]Inhibitor[/TD]
[TD]0.8198[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor II[/TD]
[TD]Non-inhibitor[/TD]
[TD]0.9067[/TD]
[/TR]
[/TABLE]

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:

​

[TABLE="class: table table-sm responsive-table, width: 0"]
[TR]
[TD]P-glycoprotein substrate[/TD]
[TD]Substrate[/TD]
[TD]0.8462[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor I[/TD]
[TD]Inhibitor[/TD]
[TD]0.6148[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor II[/TD]
[TD]Non-inhibitor[/TD]
[TD]0.8975[/TD]
[/TR]
[/TABLE]

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

[TABLE="class: table table-sm responsive-table"]
[TR]
[TD]P-glycoprotein substrate[/TD]
[TD]Substrate[/TD]
[TD]0.6133[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor I[/TD]
[TD]Inhibitor[/TD]
[TD]0.7771[/TD]
[/TR]
[TR]
[TD]P-glycoprotein inhibitor II[/TD]
[TD]Non-inhibitor[/TD]
[TD]0.8003[/TD]
[/TR]
[/TABLE]

 

[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??