Matt

You seem to have a lot of data on albumin and Phenytoin and make a 
case for doing free levels. I am not surprised at your findings. I 
did a study where I looked at Valproic acid and did albumin and both 
total and free levels. We also concluded that free levels is the way 
to go. I tried to come up with an equation correcting for albumin but 
it turned out to be very complex so it did not go any where. (Part of 
this study was published as a letter to the editor in TDM 2006).  I 
do have data and could come at it again. I would like to belive that 
we should be doing free drug levels for both these drugs (and others 
!) and develop appropriate therapeutic ranges.  Unfortunately in the 
study I did we did not have any clinical data so to develop 
therapeutic ranges was not possible. Clinically, as you are implying 
we should be doing free levels as it makes more clinical sense. I 
have been pushing for this for some time. The reason these are not 
ordered is because we (as a collective) have not come up with a 
therapeutic window. I would rather see us doing free levels and not 
get involved in correction factors or equations. But to implement 
this will require some prospective study.

bhushan

>From:    Matt Doogue <[log in to unmask]>
>Subject: Re: Phenytoin and albumin
>
>Hi Paul
>We've recently audited 5 years of phenytoin data looking at the 
>effect of albumin in about 1,000 patients (about 7,000 
>results).  The prevalence of hypoalbuminaemia was surprisingly high 
>and for >20% of  patients moved their results into or above the 
>therapeutic range i.e. changed the status of low v normal v 
>high.  We corrected for albumin assuming 90% protein binding, this 
>is simple algebra and in the literature as the Shiner Tozer 
>equation. (NB mid of our normal range for albumin is 40g/L which 
>changes the constant on the bottom line from 0.2 to 0.22).
>
>Annecdotally I see quite a few patients with clinical toxicity who 
>are treated to total phenytoing concentration without regard to 
>confounders such as albumin or coprescription of valproate.  It may 
>also partly explain the tendency of some of our colleagues to under treat.
>
>We no longer have a free phenytoin assay and when we did it wasn't 
>used much but when it's needed it's needed.
>
>We don't currently adjust for albumin although we're considering it 
>and about to discuss with our neurologists.  As to how far one goes with
>reporting calculated values or the use of alerts for confounders, 
>I'd be interested in the experience of others.
>
>Matt Doogue
>Clinical Pharmacologist
>Adelaide, Australia

bhushan

----------
Dr. Bhushan M. Kapur, D.Phil, C.Chem, FRSC, FACB, FCACB
Assistant Professor of Clinical Biochemistry
Department of Clinical Pathology, Sunnybrook Health Science Centre,
Division of Clinical Pharmacology and Toxicology, The Hospital for 
Sick Children
Department of Laboratory Medicine and Pathobiology, Faculty of 
Medicine, University of Toronto
homepage: http://www.clinitox.com

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