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Dilemma with PPK parameters

From: Varsha Mehta <varsham>
Date: Fri, 05 Feb 2010 08:58:01 -0500

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 (control-N=115).

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

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 - 08:58:01 EST

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