muaddib666
Bluelighter
- Joined
- Nov 14, 2022
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Since there's very little data available on this topic we ( me and @BosoM ) have tried to abstract it from the closest compounds that are available in both triazolo(-OLAM) and diazepine(-EPAM) forms.
The closest one metabolically are flubromazepam and flubromazolam which are also conveniently analogues of bromazepam and bromazolam respectively.
The data for the fluoro analogues are deducted from ~10 different studies and case reports.
Elimination time = 5 half-lives of the compound, at which point 96% or less of the substance can be found in blood.
Calculation table:
Flubromazolam - 28h half life
hydroxyflubromazolam - 38h (x 1,35 parent compound half-lives)
Elimination time (ESTIMATE): 190h (8 days)
Flubromazepam - 106h (3,78x longer then Flubromazolam)
hydroxyflubromazepam - 134,4h (x 1,26 Flubromazepam half-life)
Elimination time (ESTIMATE): 670h (28 DAYS)
Speculation to bromazepam / bromazolam, with relevant clinical data and some assumptions you can recalculate back to this:
bromazepam - 17h
hydroxybromazepam - 20h (x 1.2 bromazepam half life)
Elimination time (estimate): 100h (4 days)
bromazolam: 3.8h (0.22x the time of the -pam compound which makes bromazepam last around 4,4 longer then bromazolam)
hydroxybromazolam: 5h (x 1.31 bromazolam half life)
Elimination time (estimate): 24-26h (1 day~)
You can also confirm this by taking the elimination times of the fluoro analogues + metabolites (670/190)= 3.5 (flubromazepam lasts 3.5x longer then flubromazolam) and (100/26) = 3.8 (bromazepam lasts 3.8x longer in the blood then bromazolam).
This would mean that bromazolam with its main metabolite stays in your system for around 25 hours, at least.
We also considered that bromonordiazepam (desalkylgidazepam) might be a better comparison for bromazolam then bromazepam would be. Applying our calculation here, without accounting for bromonordiazepam metabolites such as the hydroxy and glucoid metabolites, because we couldn't find data for them.
bromonordiazepam: 86.7h (half-life)
Elimination time (estimate): 432,5h (18 days)
Using factor 3.78 from our flubromazepam to flubromazolam comparison.
bromazolam (86.7 / 3.78) = 22,93h
Elimination time (estimate): 114,68 (~5 days)
The lower elimination time deduced from bromazepam could be correct, as the tetrazole ring in -azolams is also susceptible to hydrolysis. But it is possible that the cyp enzyme activity increases further when switching from two to one halogen substitunent. Either way in both cases, the lactam is hydrolyzed well before the pyridine or benzene ring is attacked.
Any feedback by people with more in-depth pharmacological knowledge would be welcome!
Sources:
https://doi.org/10.1002/jms.3279
https://doi.org/10.1093/jat/bky039
https://doi.org/10.1002/wfs2.1416
https://doi.org/10.1093/jat/bkaa043
https://doi.org/10.1002/dta.2211
https://www.who.int/docs/default-so...es/43rd-ecdd/final-flubromazolam-a.pdf?sfvrsn
https://bradscholars.brad.ac.uk/bitstream/handle/10454/19320/bkad004.pdf?sequence=2&isAllowed=y
The closest one metabolically are flubromazepam and flubromazolam which are also conveniently analogues of bromazepam and bromazolam respectively.
The data for the fluoro analogues are deducted from ~10 different studies and case reports.
Elimination time = 5 half-lives of the compound, at which point 96% or less of the substance can be found in blood.
Calculation table:
Flubromazolam - 28h half life
hydroxyflubromazolam - 38h (x 1,35 parent compound half-lives)
Elimination time (ESTIMATE): 190h (8 days)
Flubromazepam - 106h (3,78x longer then Flubromazolam)
hydroxyflubromazepam - 134,4h (x 1,26 Flubromazepam half-life)
Elimination time (ESTIMATE): 670h (28 DAYS)
Speculation to bromazepam / bromazolam, with relevant clinical data and some assumptions you can recalculate back to this:
bromazepam - 17h
hydroxybromazepam - 20h (x 1.2 bromazepam half life)
Elimination time (estimate): 100h (4 days)
bromazolam: 3.8h (0.22x the time of the -pam compound which makes bromazepam last around 4,4 longer then bromazolam)
hydroxybromazolam: 5h (x 1.31 bromazolam half life)
Elimination time (estimate): 24-26h (1 day~)
You can also confirm this by taking the elimination times of the fluoro analogues + metabolites (670/190)= 3.5 (flubromazepam lasts 3.5x longer then flubromazolam) and (100/26) = 3.8 (bromazepam lasts 3.8x longer in the blood then bromazolam).
This would mean that bromazolam with its main metabolite stays in your system for around 25 hours, at least.
We also considered that bromonordiazepam (desalkylgidazepam) might be a better comparison for bromazolam then bromazepam would be. Applying our calculation here, without accounting for bromonordiazepam metabolites such as the hydroxy and glucoid metabolites, because we couldn't find data for them.
bromonordiazepam: 86.7h (half-life)
Elimination time (estimate): 432,5h (18 days)
Using factor 3.78 from our flubromazepam to flubromazolam comparison.
bromazolam (86.7 / 3.78) = 22,93h
Elimination time (estimate): 114,68 (~5 days)
The lower elimination time deduced from bromazepam could be correct, as the tetrazole ring in -azolams is also susceptible to hydrolysis. But it is possible that the cyp enzyme activity increases further when switching from two to one halogen substitunent. Either way in both cases, the lactam is hydrolyzed well before the pyridine or benzene ring is attacked.
Any feedback by people with more in-depth pharmacological knowledge would be welcome!
Sources:
https://doi.org/10.1002/jms.3279
https://doi.org/10.1093/jat/bky039
https://doi.org/10.1002/wfs2.1416
https://doi.org/10.1093/jat/bkaa043
https://doi.org/10.1002/dta.2211
https://www.who.int/docs/default-so...es/43rd-ecdd/final-flubromazolam-a.pdf?sfvrsn
https://bradscholars.brad.ac.uk/bitstream/handle/10454/19320/bkad004.pdf?sequence=2&isAllowed=y
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