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Dear all:
What important information can we get from the drug/metabolites
concentration-time profile in urine?
I know that we can calculate the renal clearance, and have an idea
about how important role the kidney plays in the elimination.
thanks all.
nina
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Several things can be determined. You can determine if the drug in
question is filtered, secreted or reabsorbed and from additionalstudies
whether the drug is protein bound.If the drug is protein bound, you may
find and increase in the clearance of other drugs or endogenous
compounds that are competively displaced by the drug. Along these same
lines you may determine if the drug alters the clearance of other
entities such as Na, K and glucose and whether the drug alters
mechanisms regulating pH.
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Nina
Sorry for the late reply - but I only just received this
(indeed I do not know if anyone else has replied already)...
> What important information can we get from the
> drug/metabolites
> concentration-time profile in urine?
Urine data in conjunction, with plasma data, can be of
considerable importance in modelling the disposition of a
drug. I have recently been working on a drug that had
parent and metabolite concentrations in plasma but no urine
data. Because of this, part of the PK model was
structurally unidentifiable and although the final model
provided an accurate representation of the data we believe
it was not a good description of the true biological fate.
Regards
Steve
=================
Stephen Duffull
School of Pharmacy
University of Queensland
Brisbane, QLD 4072
Australia
Ph +61 7 3365 8808
Fax +61 7 3365 1688
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Dear Nina,
The situation described by Steve arises quite often. Because urine data
is
unreliable in uncatheterized patients, it is often not collected. With
metabolites, amount
metabolized and volume of distribution are confounded, with respect to
plasma sampling. Similarly after an
oral dose, bioavailability and volume are confounded. Urine data can
provide you with an estimated amount renally excreted, and if you assume
all of a metabolite/parent is renally excreted, this can provide you with
an estimated amount in the body. Hence, unravelling the confounding, if
your
assumption is valid. Otherwise, it might give you a minimum amount,
aiding inference somewhat. Be careful of metabolism in the kidneys or
interconversions taking place in the urine however.
In the case where you do "know" amounts, then urine data can facilitate
calculation of renal clearance which may be useful for predicting drug
behaviour in the presence of factors affecting renal function, or even in
individualising within the normal range.
If you only have urine data, then you can estimate a compounds terminal
half-life. It may possible to do something more elaborate, but
reliable urine
collection is notoriously difficult in practise. It can be both biased
and noisy in the hospital environment, and actually consists of averaged
concentrations with sampling times determined by the patients bladder.
This may lead to systematic differences, for example a relatively well
patient may go to the bathroom and forget how precious his/her urine is to
the kineticist. A bed-bound patient may have little choice but
to
use the measuring implement. Furthermore, although plasma samples are
taken at precise times and subject to rigorous handling protocols (okay,
I'm a little optimistic) urine sampling occurs at unpredictable times and
assays may be
less reliable.
I am unsure having expressed these concerns if urine collection is a
great deal more useful than simply looking for a correlation with renal
function surrogates. Such surrogates will in any case be the most likely
clinically available information... I am open to persuasion if anyone
particularly likes urine.
James Wright
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)