RE: Dilemma with PPK parameters
Dear Varsha,
Did you evaluate the clearances as a continuous variable with changing
temperature. I suspect that the hypothermia induced was not constant over the
entire period so there may be a temperature dependent effect over the slices of
time observed with this information. I have taken the liberty of copying
Professor Poloyac at the University of Pittsburgh. This group has been
extensively involved in evaluating hypothermia effects on clearance.
Best Regards,
Rob
Robert R. Bies Pharm.D.Ph.D.
Associate Professor of Medicine and Medical Genetics
Division of Clinical Pharmacology
Member
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)
Quoted reply history
-----Original Message-----
From: [email protected] [mailto:[email protected]] On
Behalf Of Varsha Mehta
Sent: Friday, February 05, 2010 8:58 AM
To: [email protected]
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.
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
[email protected]
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