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[NMusers] Units of SIGMA estimates for urine data scaled by urine volume

From: Sarah F Cook <cook.sarah_at_utah.edu>
Date: Tue, 18 Aug 2015 12:04:07 -0400

Hi all,

I am working on a PK model that includes plasma and urine data for
parent drug and some metabolites.

The DV for the urine data are provided in concentrations (mg/L) and
scaled according to each urine sample volume (mL) as outlined in the
NONMEM Users Guide - Part V - Introductory Guide (Chapter 6, Section
9, The Output Compartment: Urine Collections and Observations; and
Chapter 7, Section 4.3.3, Scaling by a Data Item). To define the urine
sample collection time, the urine compartments are turned on with
EVID=2 and CMT=n at the start time, and turned off with EVID=2 and
CMT=-n at the end time. So the data records for each urine sample look
something like the following:

TIME EVID CMT DV UVOL
0.01 2 5 . .
3 0 5 9.03 22
3.005 2 -5 . .

And for this example, the $PK statement includes:

S5=UVOL/1000

My understanding is that NONMEM should then be scaling any
record-specific output (e.g., PRED, IPRE, RES) so that the units are
in mg/L.

My question relates to the SIGMA estimates for the urine compartments.
I have an additive component for the residual unexplained variability
of the urine compartments. Are the SIGMA estimates also scaled so
that, when expressed as a standard deviation, they should also be
interpreted as concentrations (mg/L)? Or are they not scaled so that,
when expressed as a standard deviation, they should be interpreted as
amounts (mg)? The former makes more sense to me, but I’m rather
uncertain.

A review of the literature has turned up mixed reporting practices in
this regard, so any advice would be greatly appreciated.

Kind regards,
Sarah Cook

--
Sarah F. Cook
Ph.D. Candidate
University of Utah
Department of Pharmacology & Toxicology
Center for Human Toxicology
30 South 2000 East, Room 105
Salt Lake City, UT 84112
E-mail: cook.sarah_at_utah.edu
Phone: (570) 362-2981
Received on Tue Aug 18 2015 - 12:04:07 EDT

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