Re: how to model blood volume change during and after hemodialysis?

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 > > -------------------------------------------------------------------- > > The content of this email and of any files transmitted may contain > confidential, proprietary or legally privileged information and is intended > solely for the use of the person/s or entity/ies to whom it is addressed. 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