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Re: Dilemma with PPK parameters

From: Serge Guzy <GUZY>
Date: Fri, 5 Feb 2010 09:16:44 -0800

I did not see the data but could you envisage that you have may be model misspecification. Half life relationship to clearance applies for example to the one compartmental model assumption. What if you have multiple half lives? I would not expect a simple relationship between a model using one half life with clearance when the true model has multiple one.
As far as I know the non compartmental relationship applies to clerance with volume and elimination rate and assumes linear kinetics.
Serge guzy,PhD

----- Original Message -----
From: owner-nmusers
To: nmusers>
Sent: Fri Feb 05 05:58:01 2010
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 (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

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Received on Fri Feb 05 2010 - 12:16:44 EST

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