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Dear all,
We have obtained two conc per animal in one group.There are five animals in one group. How to perform PK this.
Thanks Venkatesan
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Venkatesan,
> We have obtained two conc per animal in one group.There are five animals in one group. How to perform PK this.
Please list the times and concentrations for each animal (only 10 values!).
Tell us what route the drug was given.
Why are you want to describe PK?
Nick
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Dear Venkatesan,
It sounds like you are describing typical sparse sampling as used in Pre-clinical studies.
If you have access to Version 5 or greater of WinNonlin (current version is 6.1) then you already have access to a neat addition to the NCA module for sparse data by clicking that check box when applying the NCA model;
The method will calculate standard error for the mean concentration curve's maximum value (Cmax), and for the area under the mean concentration curve from dose time through the final observed time.
* Standard error of the mean Cmax calculated as the sample standard deviation of the y-values (i.e. Conc) at time Tmax divided by the square root of the number of observations at Tmax. * Standard error of the mean AUC will be calculated as described in Nedelman and Jia (1998), using a modification in Holder (2001), and will account for any correlations in the data resulting from repeated sampling of individual animals.
The references for these are below;
Nedelman and Jia (1998). An extension of Satterthwaite's approximation applied to pharmacokinetics. J Biopharm Stat 8(2):317-28.
Holder (2001). Comments on Nedelman and Jia's extension of Satterthwaite's approximation applied to pharmacokinetics. J Biopharm Stat 11(1-2):75-9.
Best regards, Simon. --
Simon.Davis.-at-.certara.com
Senior Scientific Consultant
Pharsight- A Certara(tm) Company
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Dear Venkatesan,
Hopefully the 2 samples/rat have been taken at different timepoints such
that when you construct a profile, there are at least 3
concentrations/time point. You can then pool the data and estimate the
variance of AUC using Bailer's method. See the reference below:
Jerry R. Nedelman, Ekaterina Gibiansky and David T. W. Lau. Applying
Bailer's Method for AUC Confidence Intervals to Sparse Sampling,
Pharm Res. 12 (1):124-128 (1995).
Good Luck,
Sury Sista
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Dear Sury and Venkatesan:
You might consider getting as data rich as you can. I don't know
Bailer's method to estimate variance of AUC, but I will look it up. I would
suggest the following:
1. Use the data to make a population model of the system you want to
describe. Make this be a nonparametric pop model. Simulate with the pop
model to get the AUC based on all the support points in the model. This will
show you a good estimate of AUC and its 95 percentile distances. You will
see the AUC's resulting from a given dosage regimen as it affects all the
genetically polymorphic support points in the model. There is no assumption
at all of a normal or lognormal distribution of the model parameters.
2. What do you plan to do with the information you have obtained? To
me, this is a question of even greater interest. Do you wish, for example,
to develop a dosage regimen to minimize the expected variation in AIC for a
subject or animal?
For a start, you might look at:
1. Bustad A, Terziivanov D, Leary R, Port R, Schumitzky A, and Jelliffe
R: Parametric and Nonparametric Population Methods: Their Comparative
Performance in Analysing a Clinical Data Set and Two Monte Carlo Simulation
Studies. Clin. Pharmacokinet., 45: 365-383, 2006.
2. Jelliffe R: Goal-Oriented, Model-Based Drug Regimens: Setting
Individualized Goals for each Patient. Therap. Drug Monit. 22: 325-329,
2000.
3. Jelliffe R, Bayard D, Milman M, Van Guilder M, and Schumitzky A:
Achieving Target Goals most Precisely using Nonparametric Compartmental
Models and "Multiple Model" Design of Dosage Regimens. Therap. Drug Monit.
22: 346-353, 2000.
4. Jelliffe R, Schumitzky A, and Van Guilder M: Population
Pharmacokinetic / Pharmacodynamic Modeling: Parametric and Nonparametric
Methods. Therap. Drug Monit. 22: 354-365, 2000.
Software is available to do this at www.lapk.org. Click on software, clock
on downloads, put in your contact information, and we will send you an email
giving you permission to access it. It is then available for a modest
donation.
Very best regards,
Roger Jelliffe
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