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RE: Dilemma with PPK parameters

From: Bies, Robert R. <rrbies>
Date: Fri, 5 Feb 2010 10:05:03 -0500

Dear Varsha,

Did you evaluate the clearances as a continuous variable with changing temp=
erature. I suspect that the hypothermia induced was not constant over the =
entire period so there may be a temperature dependent effect over the slice=
s of time observed with this information. I have taken the liberty of copy=
ing Professor Poloyac at the University of Pittsburgh. This group has been=
 extensively involved in evaluating hypothermia effects on clearance.

Best Regards,


Robert R. Bies Pharm.D.Ph.D.
Associate Professor of Medicine and Medical Genetics
Division of Clinical Pharmacology
Center for Computational Biology and Bioinformatics
Indiana University School of Medicine
1001 W 10th Street W7138
Indianapolis, IN 46202
317-630-7868 (office)
317-630-8185 (fax)

-----Original Message-----
From: owner-nmusers
 Behalf Of Varsha Mehta
Sent: Friday, February 05, 2010 8:58 AM
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 on=
e group had induced hypothermia (treatment-N=24) while the other did not=

The half life for control- 111hrs and treatment 129 hrs (roughly)- not stat=
istically 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 th=
e model. I have run the model for both multiple times using various theta v=
alues. each time the minimization is complete. The bootstrap for treatment =
group gives reasonably good agreement. The bootstrap for control parameter=
s 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

Electronic Mail is not secure, may not be read every day, and should not be=
 used for urgent or sensitive issues
Received on Fri Feb 05 2010 - 10:05:03 EST

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