RE: Dilemma with PPK parameters
Dear all,
Just a short note:
There is still a relationship between CL and half-lives for a two-compartmental
model although not as simple as for a one compartmental model.
For a two-compartmental model you can derive the two half-lives (t1/2alpha and
t1/2 beta) through either estimates of macro (CL, V2, V3, Q) or micro constants
(K10,K21,K12) through (2 comp iv model):
K10=CL/V1
K12=Q/V1
K21=Q/V2
SUM=K10+K12+K21
ROOT=SQRT(SUM*SUM-4*K21*K10)
Alpha=0.5*(SUM+ROOT)
Beta=0.5*(SUM-ROOT)
t1/2alpha=LN(2)/Alpha
t1/2beta=LN(2)/Beta
Best regards,
Ulrika
Ulrika Simonsson, PhD
Assoc Prof of Pharmacometrics
Uppsala Pharmacometrics
Department of Pharmaceutical Biosciences
Uppsala University
BMC, Box 591, 751 24 Uppsala
Sweden
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Serge Guzy
Sent: den 5 februari 2010 18:17
To: [email protected]; [email protected]
Subject: Re: [NMusers] Dilemma with PPK parameters
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.
Best
Serge guzy,PhD
President,CEO,POPPHARM
----- Original Message -----
From: [email protected] <[email protected]>
To: [email protected] <[email protected]>
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.
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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