Units of SIGMA estimates for urine data scaled by urine volume

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: [email protected] Phone: (570) 362-2981