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Hi everyone,
I am interested in getting some feedback about what the best approaches are to analyze sparse tissue
sampling data. What is the best approach/es to estimate tissue PK parameters, to compare exposures
across different tissues and to assess the variability in this exposure? Is a particular analytical
method (NCA/Bailer vs. bootstrap vs. POPPK modeling) preferred over another when dealing with such
sparse data (tissue PK profiles constructed from pooled samples where each subject may contribute to
more than one data point)? If anyone has any suggestions it would be greatly appreciated. Thank you
in advance.
Shalini (syapa.at.unc.edu)
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Hi Shalini,
Excellent question. In my opinion, such data are best analysed via
either the bootstrap method from Mager and Göller (J Pharm Sci 1998;
87:372-8) or by population PK modelling, as you wrote. I have a feeling
that population PK modeling might be more robust, if your quantification
limit is relatively high. If you have nonlinear PK, pop PK modeling seems
the way to go.
Both approaches have pros and cons. However, it is important to note that
standard non-compartmental analysis makes many assumptions which
are also made by compartmental modeling as summarized previously
(Bulitta & Holford, An Introductory Guide To Non-Compartmental Analysis,
Wiley Encyclopedia of Clinical Trials, 2008; p. 1-21).
Please let me know, if you need help to set this analysis up in a
modeling software.
Best wishes
Juergen
Jurgen Bulitta, PhD
Senior Research Fellow
Australian Research Council DECRA Fellow
Drug Delivery, Disposition and Dynamics
Faculty of Pharmacy and Pharmaceutical Sciences
Monash University
Email: Jurgen.Bulitta.-at-.monash.edu
Adjunct Assistant Professor,
SUNY at Buffalo, Buffalo, NY, USA
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Hi all,
As a follow-up to the question from Shalini, I would like your opinion on a related issue.
When dealing with plasma data we estimate (using a.o. PopPK modeling) an apparent volume of
distribution to account for drug distribution.
Because we are only sampling a fraction of the total apparent distribution volume and the
distribution volume in itself is not measurable, this makes sense.
However, when we collect a known amount of tissue (e.g. 25 mg) and drug concentrations are
determined using an analytical method that recovers 100% of the drug present within the tissue,
should we then estimate the volume of distribution or fix the volume of distribution to the weight
of the collected tissue?
Kind regards,
Pieter Colin
--
Pieter Colin, Pharmacist
Ph.D. Student (Pre-) Clinical Pharmacokinetics & Pharmacodynamics
Laboratory of Medical Biochemistry and Clinical Analysis
Faculty of Pharmaceutical Sciences
Ghent University
Ottergemsesteenweg 460
B-9000 Gent
Belgium
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Dear Peter:
I would relate it to the weight as you suggest. We measure serum concentrations, but the drug
that is elsewhere, we cannot know the concentrations, only the estimated amount in the peripheral
nonserum compartment. In our model for digoxin where we have a peripheral nonserum compartment, this
is what we do. Serum concentrations are ng/ml, peripheral concs are in ng/gm.
Best to all,
Roger Jelliffe
Roger Jelliffe
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