RE: PAMAM-OH nanoparticles
Dear Olinto,
I do not think that your suggestion on grouping the observations as if they
originated from only five different mice is a good idea. How would you then
interpret the random effects? What mice would be grouped together?
However I wonder, cannot the nanoparticles be quantified in plasma and
wasnt that sampled in any mice up until the sacrificing? The plasma PK of
the nanoparticles should if I dont completely misunderstand the project be
closely related to the biodistribution in one or several organs/tissues. If
multi sample plasma PK and single sample tissue concentration was modeled
simultaneous a large part of the problem with single sample tissue
observations could be avoided. You likely still couldnt separate the
between mice variability in any parameter exclusively describing the rate of
a tissue distribution from the residual error (unless you make some fairly
strong assumptions regarding the residual error) however the variability in
tissue concentration will likely be largely dependent on variability in
processes also affecting the plasma concentrations.
Kind regards,
Martin Bergstrand, PhD
Pharmacometrics Research Group
Dept of Pharmaceutical Biosciences
Uppsala University
Sweden
Postal address: Box 591, 751 24 Uppsala, Sweden
Phone +46 709 994 396
Fax + 46 18 4714003
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Fidler,Matt,FORT WORTH,R&D
Sent: Thursday, June 02, 2011 7:43 PM
To: [email protected]; [email protected]
Subject: RE: [NMusers] PAMAM-OH nanoparticles
Olinto,
Hing et al reported using mixed-effect modeling instead of fixed effects
modeling to characterize data (and may reduce parameter bias). However,
this method still does not characterize between animal variability.
Matt.
Hing, J. P.; Woolfrey, S. G.; Greenslade, D. & Wright, P. M.
Is mixed effects modeling or naïve pooled data analysis preferred for the
interpretation of single sample per subject toxicokinetic data?
J Pharmacokinet Pharmacodyn, Department of Anaesthesia, University of
Newcastle upon Tyne and Alnwick Research Centre, Sanofi, Alnwick,
Northumberland., 2001, 28, 193-210
From: [email protected] [mailto:[email protected]] On
Behalf Of Olinto Linares
Sent: Thursday, June 02, 2011 12:04 PM
To: [email protected]
Cc: [email protected]
Subject: [NMusers] PAMAM-OH nanoparticles
Dears NMusers
PAMAM Nanoparticles used as anticancer drug carrier.
During a biodistribution study 5 mice were sacrificed at each sample time,
5, 30, 60, 120 minutes, and 6, and 24 hours, after a bolus infusion of
50mg/kg of PAMAM-OH.
We are interested in the PAMAM-OH kinetics.
Can we apply population pharmacokinetics analysis on these types of data?
(i.e grouping the data as if they came from only 5 mice that were sampled at
those times)?
looking for ideas, suggestions
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