Depakote adjusted for low albumin

[heyjack70]

Anyone heard about a specific formula for calculation of a depakote serum level if patient has low albumin? Saw this mentioned on another psychiatrist's note from several years ago. I've read about equations for adjusting based on Phenytoin, and read general statements that "low albumin" can increase free depakote (unbound to albumin fraction) by 2 x. Also, anyone heard of pregabalin for Tardive Dyskinesia?

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[VMSmith]

Hermida and Tutor, A Theoretical Method for Normalizing Total Serum Valproic Acid Concentration in Hypoalbuminemic Patients, J Pharmacol Sci 97, 489 – 493 (2005)

 

[heyjack70]

Thanks.

So they give you a reference table and an equation. For example, a patient with valproic acid level of 106 and albumin 3.1 g/dL has a normalized total valproic acid level of about 228. Which is of course above the reference range I'm usually comfortable with when treating bipolar.

Does anyone check free valproic acid levels on a regular basis? It seems like would be the gold standard test, but I don't think I've ever seen that done. Maybe it's expensive.

 

[Merovinge]

I am curious about this as well, I know the studies used to demonstrate Depakote effectiveness just use total levels, but it appears the drug has pretty complex protein binding (that is to say, non-linear), which would make me think free levels would be more helpful in determining appropriate titration?

 

[LimbicResponse]

While the thought is a good one, the references ranges were created from total levels and span the spectrum of most albumin states. We would need new reference ranges if we used
"Free depakote" and I'm not even sure it would be helpful.

 

[notdeadyet]

"Free depakote"

I think I've seen this on a tee-shirt...

 

[kugel]

My memory on this is a little fuzzy, so I'd appreciate some feedback. I seem to remember that Depakote is almost completely bound up to a level around 50, and that's a large part of the reason why that is considered the low end of the therapeutic range. It doesn't even become free until that level. and that this is why we don't need a "free depakote" level, b/c below 50 the "free" portion is near zero, and above 50 you're looking for clinical benefit vs SE's more than a particular concentration.

 

[heyjack70]

My memory on this is a little fuzzy, so I'd appreciate some feedback. I seem to remember that Depakote is almost completely bound up to a level around 50, and that's a large part of the reason why that is considered the low end of the therapeutic range. It doesn't even become free until that level. and that this is why we don't need a "free depakote" level, b/c below 50 the "free" portion is near zero, and above 50 you're looking for clinical benefit vs SE's more than a particular concentration.

...and thus, a reasonably sounding urban myth was born. Sounds reasonable to me.