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Re: Dilemma with PPK parameters

From: tgordi
Date: Mon, 8 Feb 2010 13:26:41 -0500

Hi Varsha,

Continuing on Ken's response, have you tried a simple model without any
covariates? Do you get the same values
for CL as you do with the control stream you provided? Could you also provi=
de the
values for all the four THETAs you estimate in your control stream?


On Fri 02/05/10 8:58 AM , "Varsha Mehta" varsham
> 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.
> Thanks!!
> 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 Mon Feb 08 2010 - 13:26:41 EST

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