Nele,
You can use T in $DES block if you use ADVAN6, 8, 9, or 13 and write you
system in differential equations
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
On 1/18/2013 10:12 AM, Kaessner, Nele wrote:
Dear Ahmed and all,
First of all, thank you for your response.
The reason I believe that blood volume is altered is because I see an increase
in concentrations until the end of hemodialysis, despite the fact that compound
infusion ended two hours earlier. I would want to estimate the decreasing
volume using information from both subjects with and without hemodialysis (for
those without dialysis, concentrations drop as expected after the end of the
infusion). Clearance via hemodialysis is not a problem by the way, compound is
too big :-)
My problem mostly relates to the coding in NONMEM. How do I model a continuous
change in V1 over time? $PK does not allow the variable 'T' to be used, and I
don't just want to use TIME, as this would only consider time points actually
contained in the data set.
Any suggestions?
Thank you and best regards
Nele
______________________________________________________________
Dr. Nele Käßner
Principal Scientist Modeling and Simulation
Global Pharmacometrics
Experimental Medicine
Takeda Pharmaceuticals International GmbH
Thurgauerstrasse 130
8152 Glattpark-Opfikon (Zürich)
Switzerland
Visitor address:
Alpenstrasse 3
8152 Glattpark-Opfikon (Zürich)
Switzerland
Phone: (+41) 44 / 55 51 404
Mobile: (+41) 79 / 654 33 99
mailto: [email protected]
http://www.takeda.com
-----Original Message-----
From: Ahmed N Mohamed [mailto:[email protected]]
Sent: Freitag, 18. Januar 2013 3:28
To: Kaessner, Nele
Cc: [email protected]
Subject: Re: [NMusers] how to model blood volume change during and after
hemodialysis?
Hello,
In terms of how long it takes to restore blood volume, i think it should be
immediate because they usually give fluids during the dialysis to replace lost
blood volume. Otherwise, there will be a significant drop in BP. You may have
the volumes of fluid given in the patient charts if you have that.
In terms of changing volume you can do that in two ways:
1. If you have serial measurements of patient body weight, you can link that to
volume as a covariate and it will change with change in weight (time-varying
covariate). But this needs hourly or even more frequent weight measurements.
2. You can model the change in volume with time using a simple linear slope
model where volume decreases with time during dialysis and increases with time
after dialysis and estimate the slope for each process. However, i think this
will be difficult to estimate separate from changes in clearance and the slope
estimates you get will just be arbitrary. If you have samples from dialysate,
it might be better.
I hope this helps.
----- Original Message -----
From: "Nele Kaessner" <[email protected]>
To: [email protected]
Sent: Friday, January 18, 2013 8:24:05 AM
Subject: [NMusers] how to model blood volume change during and after
hemodialysis?
Dear nmusers,
I would like to model PK profiles of a compounds which mostly distributes in
blood volume. The subjects which were investigated underwent hemodialysis for
approx. the first three hours after infusion start, and the compound was given
over a time period of ~5-10 min.
It is well known that during hemodialysis, blood volume changes. Therefore, I
would like to add a dynamic component to the central volume parameter, allowing
it to decrease during hemodialysis and then to reincrease after dialysis has
ended. I have all information about start and end time of both dosing and
dialysis. Individual times between subjects differed. Unfortunately, I have not
been creative enough to come up with a NONMEM code that can do this. Could any
of you help out?
Also, I probably do not have late enough time points to estimate when exactly
blood volume would be restored. Does anyone know how much time the body needs
after dialysis has ended until it is back to the original blood volume?
Thanks for your help and best
Nele
______________________________________________________________
Dr. Nele Käßner
Principal Scientist Modeling and Simulation
Global Pharmacometrics
Experimental Medicine
Takeda Pharmaceuticals International GmbH
Thurgauerstrasse 130
8152 Glattpark-Opfikon (Zürich)
Switzerland
Visitor address:
Alpenstrasse 3
8152 Glattpark-Opfikon (Zürich)
Switzerland
Phone: (+41) 44 / 55 51 404
Mobile: (+41) 79 / 654 33 99
mailto: [email protected]
http://www.takeda.com
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