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

Van: [email protected] [mailto:[email protected]] Namens Kaessner, Nele Verzonden: vrijdag 18 januari 2013 16:13 Aan: Ahmed N Mohamed CC: [email protected] Onderwerp: RE: [NMusers] how to model blood volume change during and after hemodialysis? 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. If you have received this email in error you have no permission whatsoever to use, copy, disclose or forward all or any of its contents. 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