RE: Best approach with limited data
Hi,
The number of parameters, both the structural PK model and the
statistical model, would depend on the number of subjects and data
points as well as when they were collected in relation to the actual
time-course of the drug in both plasma and tissue. If your sampling time
provides enough information on a 2-comp model for each specimen, I don't
see why there would be any problems estimating the parameters. I am
uncertain if you can estimate any reliable parameters for your error
model since you only have 1 sample per subject.
What you might want to do is to make a graph of all your data and check
if you can "see" a bi-exponential conc.-time curve in both specimen.
Alternatively, make a graph of the mean values at each time-point and
check for the shape of the curve. Then start with the simplest model in
your plasma samples and continue to build it up with tissue data. For
the simple model, I would suggest using 1 ETA on the most plausible
parameter (CL or VC). You can always test addition of more ETAs once you
have your structural PK model in place.
Toufigh
Quoted reply history
________________________________
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED]
On Behalf Of Mulla Hussain - Senior Pharmacist
Sent: Wednesday, February 28, 2007 8:57 AM
To: [email protected]
Subject: [NMusers] Best approach with limited data
Hi
I have sparse data from n=69 individuals from 3 dose levels, and rich
data from 1 individual at 1 dose level, following the deployment of a
drug eluting device. In the 69 individuals I have a single plasma
sample, and a single tissue sample (both collected at the same time
point). The sample time points range from 0.25 to 120 days (post
deployment), 2 individuals contributing at each time point. In the 1
individual I have greater than 8 sample points in each biophase.
The rich data from the 1 individual suggests 2 compartment disposition
in both plasma and tissue (a 4 compartment model described the data
quite well in WinNonLin). Pooling the sparse data at each dose level,
suggests 2 compartment disposition in both blood and plasma. My
questions are:-
1) Would you take a population approach to this data? - can mean
population parameters and their variability be robustly estimated?
2) Would you expect the parameters of a 4 cmpt model (8 thetas and
at least 4 omegas) to be reliably estimated with this data?
Any thoughts much appreciated.
Thanks
Hussain Mulla
Department of Pharmacy
University Hospitals of Leicester NHS Trust
Glenfield Hospital
Leicester
England
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