Displacement of protein bound etizolam (or other benzos) with aspirin?

[Naggers]

So, I read in a textbook in the library today that diazepam is highly protein bound, and that taking aspirin (higher protein binding affinity) will displace the diazepam resulting in a greater physiological effect.

This got me thinking, would this be the case for all highly bound benzos? Knowing that alprazolam and etizolam (first two benzos which come to mind) are both highly protein bound, I was wondering if taking an aspirin or two after my dose kicks in would make a difference, get me more bang for my buck.

Any thoughts?

 

[MikeRWK]

Could this also work with phenibut?

 

[23536]

Source?

Makes sense theoretically, but I'm not finding any solid info on it. Measurements would be nice. Something like:

Br J Clin Pharmacol. 1982 Apr;13(4):553-60.

Valproic acid and diazepam interaction in vivo.

Dhillon S, Richens A.

1 The effect of oral administration of sodium valproate (1500 mg daily) on the distribution and elimination kinetics of intravenously administered diazepam in six healthy volunteers has been studied. 2 During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N-desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.

 

[Naggers]

Well, when I say 'today', it was actually last week and I've been thinking about it since. I have also tried a few _brief_ google searches and found very little.

Would have done some more searching after posting last night but I decided to take some etizolam and only woke up an hour ago :D
Interestingly (or perhaps placebo-ily), I took an aspirin just after I woke up and am now starting to feel a bit wonky. Anecdotal evidence at its best!

Anyway I'll do a good long search tonight or tomorrow if I have the enthusiasm (2 projects to do today and full day of lectures&labs tomorrow), was just wondering if any ADDers had any previous knowledge on this.

Thanks for that source, 235360287471352662. Looks like we might be on to something here.

(Edit: not sure about phenibut Mike, same basic theory as this though I guess, if I understand the theory correctly then you just need something with a higher protein binding affinity to displace it. Though I'm still learning so don't take my word on it. Smart people please feel free to correct me!)

 

[skillet]

Interesting, I figured there would be plenty of albumin to easily mop up a dose of a benzo and aspirin. But with an average of 44g/L, and an average of 2.5L of serum giving a person something like 110g of albumin, that's only about 1.6 mmol. Wonder how many drug molecules each protein molecule can bind?

 

[dip12]

Sounds like a recipe for a stomach ulcer.

 

[Naggers]

Well I was hoping that sub-stomach ulcer doses would be enough for a noticeable effect.

Also, I'm starting to think I should have put diazepam instead of etizolam in the title of this thread and maybe it would have more responses :D

200+ views within a few hours isn't bad though. I'm just surprised none of you have come across this before or have an answer. I was expecting it to either be a dumb question or one that's been covered plenty. I'm itching to do some research on it but I still have a lab report on plant lectin haemagglutination to write for tomorrow

 

[Hammilton]

best suggestion? Give it a try. If you're using nothing but benzos you won't be at risk of dangerously over-doing it, at least.

 

[Torabora]

over dose is very very unlikely as there is no drug interaction known and since benzos&aspirin are widley used there must be thousands of cases were people combined this 2 compunds so the effect, if present must be very weak, or the dose of aspirin must be very high, else this would have already be explored.