NONMEM Users Network Archive

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RE: Time varying volume of distribution implementation

From: R.terHeine
Date: Mon, 25 Apr 2016 07:49:23 +0000

Dear Thorsten,

As suggested by other, implementing a time dependent covariate in $DES should be the way to go. A quick workaround could also be inserting dummy observations at regular intervals in your dataset e.g. when using ADVAN5.

Just out of scientific curiosity:
Are you investigating total (maternal + fetal) body weight as a covariate for volume of distribution? I would expect that both maternal body weight (water retention and increase in fat tissue) and placental-fetal-weight (growth, increase in volume of amniotic fluid) may increase during pregnancy and that depending on the drug (whether it penetrates the placenta) this has implications for your analysis.



Dr. R. ter Heine, hospital pharmacist-clinical pharmacologist
Head of Clinical Trials Unit, Dept. of Pharmacy

Van: owner-nmusers
Verzonden: vrijdag 22 april 2016 23:34
Aan: nmusers
Onderwerp: [NMusers] Time varying volume of distribution implementation

Dear NMusers,

I'm modeling a compound where body weight has a known impact on the volume of distribution. This compound is investigated in pregnant women over a long period (from gestational age of 8 weeks until they give birth). Consequently, the body weight changes over time and I have a decent formula to describe the individual body weight change. The PK model has to be coded by ODEs. Does anyone has experience how to integrate a time varying volume of distribution if differential equations are used?

Best regards



Thorsten Lehr, PhD

Junior Professor of Clinical Pharmacy

Saarland University

Campus C2 2

66123 Saarbr├╝cken


Office: +49/681/302-70255

Mobile: +49/151/22739489

thorsten.lehr ehr<>

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.
Received on Mon Apr 25 2016 - 03:49:23 EDT

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