• N&PD Moderators: Skorpio | thegreenhand

  • Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

How much does Tranxene accumulate ?

K

Kdem

Bluelighter
Joined
Mar 14, 2015
Messages
334
Although I did look for answer I'm still mostly clueless.

While the half life is more or less known, the answer to my question is not.
Diazepam accumulates to 5-8 times the daily dose. (for clonazepam, that's three times the daily dose)

Diazepam tends to sit in fat cells.

Tranxene's metabolite desmethyldiazepam is also lipophilic, but I cannot find anything about accumulation after repeated dosing. Anyone ? I wonder if it accumulates the way diazepam does.
 
Last edited:
Although I could only read the abstract, I didn't see anything about any specifics regarding the accumulation of desmethyldiazepam in tissues after the administration of Tranxene. I know about the long half life, but does it accumulate in the kidneys, heart, fat like diazepam does (which causes excessive accumulation, after taking diazepam for some time it can take up to two months to get the diazepam and its metabolites out of the body) ?
 
Top right, click pdf for whole study. The data is there but its confusing a bit. And its an old paper but many on the kinetics of benzos are.
 
Maybe it's me, but I don't see that for desmethyldiazepam from Tranxene. Only from diazepam. I hope you don't expect me to understand table 1 ... Nothing as clear-cut as 'accumulates to X times the daily dose'. I will re-read later.
If you can finish what you posted in that other thread I'd appreciate it :)
 
Last edited:
I will eventually, hopefully later today. In this particular study they say clorazepate is metabolized 50% to desmethyldiazepam and that it fits their model (5 compartments, the grad students doing the calculations must have had fun :) ) for distribution and accumulation of diazepam. When I get a chance, I will try and highlight the sections.
 
Too lazy to read the study again, but doesn't Tranxene convert to desmethyldiazepam at a rate of 100 % ? If not, what does the other half go to ?
I think that 50 % of diazepam is converted to desmethyldiazepam.
 
Kdem said:
Too lazy to read the study again, but doesn't Tranxene convert to desmethyldiazepam at a rate of 100 % ? If not, what does the other half go to ?
I think that 50 % of diazepam is converted to desmethyldiazepam.
Click to expand...

wikipedia says that clorazepate is completely metabolized to nordiazepam in the gastrointestinal tract, otherwise benzos usually get hydroxylated on the phenyl or benzodiazepinic ring and then conjugated (to be eliminated) but this can happen only after the passage of GI tract
 
Yeah, that was dumb of me. It says 50% of diazepam is metabolized into desmethyldiazepam. I will read it more carefully as I really wasnt looking for the clorazepate info but trying to find same of the distribution constants for our other discussion, Kdem. Ive read so many benzo PK papers recently I feel like I am on Valium and benzos really arent my thing nor do I find them particularly interesting. Sorry.
 
Kittycat5,

I'm still interested in the question if Tranxene accumulates the way diazepam does. I didn't see it in that paper, but what do I know. I get that it takes up to two months to get diazepam and its metabolites out of the system. And that diazepam accumulates up to 5-8 times the daily dose after extended dosing. (While clonazepam just accumulates to three times the daily dose, despite a somewhat similar half life, 1-2 days)
I understand if you've had enough of this benzo stuff.
 
After chronic administration, desmethyl diazepam (nordiazepam) has a T½ of 200 hours, 8 days more or less.
 
clubcard, I've seen other numbers as well.
Aside from that issue, again: diazepam accumulates to 5-8 times the daily dose (half life:1-2 days), it can take two months to get the drug (including metabolites) out of the body after extended dosing.
While clonazepam has a half life of 1-2 days, and with once daily administration it accumulates to three times the daily dose.

EDIT: clubcard, where did you get that number of '200 hours' ? I've seen stated half lives of 50-200 hours, the latter for the 'elderly'. 200 hours is incredibly long, compared to diazepam's 1-2 days and clonazepam's 1-2 days.
 
Last edited:
All Tranxène is metabolized into demethyldiazepam, which has a half life of 50-200 hours. Diazepam is also metabolized to oxazepam and temazepam, which have considerably shorter half lives, that might explain why diazepam, at least theoretically, has a shorter half life then Tranxène (clorazepate).

Tranxène is extensively used in acute psychiatry in the Netherlands. It's rapid acting orally and also comes in injectable form (50 mg tablets and powder for injection). I can assure you it does accumulate, I've seen this happen multiple times. Problems with accumulation make most pdoc's prefer lorazepam as the general use benzo for sedation in agitated patients. Fun fact is that Tranxène is more potent orally then IM.
 
Well, I know that diazepam has a complicated accumulation (up to 5 to 8 times the daily dose). In most cases a rule like 5 X half life works for (near) complete elimination. While diazepam has a half life of 1-2 days, after repeated accumulation it can take a very long time to get the drug out of the body. Including its metabolite desmethyldiazepam, two months.
For clonazepam it´s two weeks tops.

I´m not sure how that works for Tranxene or desmethyldiazepam as the primary drug. Does anyone ?

Wizzle, regarding your statement in your second paragraph: I did try Tranxene for two days. A straight switch from clonazepam to Tranxene. And I am puzzled.
I had expected it to last longer than diazepam ('duration of action', not 'half life'). Aside from the fact that it was weaker than diazepam, it was much shorter acting. I felt a peak of about one to two hours, then it seemed to peter out. Of course, there was still plenty of clonazepam left in my system.
It seems that many people can take it twice a day, while I would have interdose withdrawal.

Any comments on why it would be shorter acting ?
I did get the impression that after the initial 'duration of action' phase the long half life still did something, especially on the second day. Redistribution ?
I wonder why this drug is used extensively in acute psychiatry in the Netherlands ?
 
Last edited:
It's used because it's rapid acting (oral Tmax is 45 minutes) and available in both oral and IV/IM form, a necessity for acute psychiatry. In the Netherlands the only benzo's available in injectable form are lorazepam, diazepam, clonazepam, clorazepate and midazolam. Clorazepate and lorazepam are the only benzo's commonly given parenterally in psychiatry. Diazepam only comes in 10 mg dose, which is inconvenient, same goes for clonazepam, which only comes in 1 mg dose. Midazolam isn't commonly used because psychiatrists are scared of adverse events. So that leaves lorazepam and clorazepate.

When starting a drug like Tranxene you would have to take it at least three times a day, preferably four. Otherwise redistribution will leave you undertreated in between dosing intervals. As soon as you reach a steady state you can probably get away taking it twice a day or just at night for example.
 
Interesting.

Is there any real evidence (personal experience?) that the accumulation will make up for the relatively short duration of action of a dose ? I can see the logic, I'm just not sure if it works that way.
 
You must log in or register to reply here.
Top