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Dear All,
I have data regarding Concentration parent drug vs Time and
Concentration metabolite vs time--- obtained from an IV dose of the
parent drug assuming first order process for the metabolite to be
formed.
Is it possible to calculate Vd and clearance of the metabolite? or do
you think that I need data after an IV dose of metabolite itself?
Thanks
M.
[I think you will find that you need urine data to help with those
calculations. See:
http://www.boomer.org/c/p3/c20/c2005.html
- db]
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The following message was posted to: PharmPK
Dear M. :)
If you have concentrations of parent and metabolite, you can estimate
all model parameters if you assume 100% (or any other fixed fraction)
conversion of parent to metabolite. Alternatively, sometime it is
assumed that volume of parent = volume of metabolite. In this case
fraction of parent converged to metabolite can be estimated. In any
case, validity of the assumptions should be justified. Also, the
system should be solved in mole units, or ratio of parent to
metabolite molecular weights should be accounted for in the model.
Leonid
--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
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Dear Leonid,
Many thanks for your answer.
If I assume V = Vm and then I calculate metaboilite clearance, how
accurate will this value be? will I be able to say anything about the
clearance of metabolite relative to the clearance of the parent drug?
Thanks in advance
Regards
MONICA :)
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Dear Monica,
If you assume V = Vm (when you model parent and metabolite data)and
then calculate metabolite clearance, the value will be as accurate as
your assumption. If this assumption is correct, then you will get
correct values of metabolite clearance (and correct estimates of
fraction on the parent drug converged to metabolite: it should be
included into the model and estimated if you use V = Vm assumption).
If the assumption is not valid, your estimates will not be valid
either. You can use estimated fraction of parent-to-metabolite
convergence as an implicit test of this assumption: it should be
reasonable (in terms of what you know about this or similar drugs).
The situation is somewhat similar to the oral administration of the
drug: you can only estimate (metabolite) apparent clearance and volume
CL/F and V/F, where F in this case is the fraction of the parent
converged to metabolite (similar to the bioavailability in the oral
administration case). If you know F, you can get CL. V=Vm assumption
allows you to estimate F but the estimate is only as good as your
assumption.
Leonid
--
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
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Dear Monica et al -
Just trying to learn out here... What's the advantage of calculating
these parameters from dosing the parent? (other than saving yourself
one experiment.)
I am just curious what's the situation in your case that makes you go
in this direction rather than measuring the PK dosing the metabolite
and getting your parameters in the absence of parent...
Looking forward to your responses - thank you
Dario
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I am also trying to learn from this: in what way would these assumptions
be affected by where the metabolite is being formed? Is the default
assumption that metabolites are being formed in the central compartment?
Best regards,
Frederik Pruijn
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The following message was posted to: PharmPK
Dear Dario,
I am currently doing a postgraduate course, and calculating clearance
and Vd of the metabolite using parent data was one of the questions
of the assigment I had to do. Therefore, this is not a real case.
As I could not find the answer in any book, I decided to ask the
experts and put the question in the forum.
Kindest regards
MONICA
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