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Does anyone have any experience on the validity of spot tests for
6-hydroxycortisol to cortisol ratios in urine. I've seen two published
papers. One says that there is a circadian rhythm, the other says there
isn't. I would suspect that if you kept the time of sampling to the same
time of day then spot tests would be pretty reliable. Does anyone know
otherwise?
Thanks.
Peter L. Bonate, PhD
Director, Pharmacokinetics
ILEX Oncology, Inc
4545 Horizon Hill Blvd
San Antonio, TX 78229
email: pbonate.-at-.ilexonc.com
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Peter,
The 6-OH-C/C ratio is also highly variable. If you design your study to
increase confidence on the baseline values and you keep time of day a
constant, you should be OK. There is substantial diurnal variation and
if you have placebos in your study, you should get a good handle of the
ratio in drug naive subjects.
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Dear Peter,
Quite frequently the use of urinary6-beta-OH cortisol/cortisol ratio as
a "shortcut" to proper studies evaluating possible 3A4 interactions
emerge. People tend to believe that if this ratio is not
changed during treatment, the compound is not a substrate for 3A4. Since
I have been working a lot with cortisol, I have my doubts about the
specificity of this ratio. Certainly 3A is involved in the metabolism of
cortisol, but there are also other enzymes involved in cortisol
metabolism. In addition to that, the dramatic diurnal variations in the
production of cortisol complicates the picture. I noticed a recent paper
in Br J Clin Pharmacol (Boulton et al) where some criticism is given.
With the recent data on CYP3A5 (Nature Genetics, April) the whole area
of measuring 3A4 vs 3A5 and their interrelationship with p-gp now
becomes even more complex.
All I can really say about the 6-beta OH/cortisol ratio is to confirm a
caution - it is quick and potentially very dirty.
Bets regards
Anders Grahnen
Anders Grahnen, Ph.D.
Professor
Vice-President, Director R&D
Quintiles AB
Islandsgatan 2.
S-753 18 UPPSALA, Sweden
anders.grahnen.aaa.quintiles.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)