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RE: Dilemma with PPK parameters

From: Mats Karlsson <mats.karlsson>
Date: Mon, 8 Feb 2010 20:18:52 +0100

Dear all and dear Varsha,

There are so many problem posed to this list that could be sensibly answered
if a control file had been attached. This is probably one of them. Please
provide model files if you are asking questions about why your model doesn't
work (sometimes also a small portion of the data set is needed). The list
has many contributors that are eager to help, why not giving them an honest
chance of doing so. Providing model files could also be instructive to
others, I often learn new coding possibilities and clever ways of doing
things by reading code from others.

Finally, it is always appreciated to learn if and how the problem was

Best regards,

Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003

-----Original Message-----
From: owner-nmusers
Behalf Of Varsha Mehta
Sent: Friday, February 05, 2010 2:58 PM
To: nmusers
Subject: [NMusers] Dilemma with PPK parameters

Dear Group:
I am seeking some help to logically explain the difference in CL of a drug
between 2 groups who received the same drug for the same indication but one
group had induced hypothermia (treatment-N=24) while the other did not

The half life for control- 111hrs and treatment 129 hrs (roughly)- not
statistically different.
However, the parameters:

Control Group Treatment group

CL- 0.000105 L/kg/hr (suspect) CL- 0.00467 L/kg/hr


Vd -0.733 L/kg Vd 0.876 L/Kg

I used the same model for both groups and the half life calc was part of the
model. I have run the model for both multiple times using various theta
values. each time the minimization is complete. The bootstrap for treatment
group gives reasonably good agreement. The bootstrap for control parameters
match well for Cl (0.000273 L/kg/hr) but not for Vd (0.416 L/kg).

 Given the relationship between Vd and CL how is this possible? How can the
half life be so close when there is such a huge difference in CL for both
groups? Where am I going wrong?

Would appreciate any help anyone can provide.


Varsha Mehta, MS(CRDSA), Pharm.D., FCCP
Clinical Associate Professor
Pharmacy, Pediatrics and Communicable Diseases Clinical Pharmacist Neonatal
Critical Care University of Michigan
(O) 734-936-8985
(F) 734-936-6946

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Received on Mon Feb 08 2010 - 14:18:52 EST

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