NONMEM Users Network Archive

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questions about IOV

From: Jia Ji <jackie.j.ji>
Date: Tue, 10 Nov 2009 21:02:36 -0500

Dear All,

I am a new NONMEM user and now trying to model clnical PK data with a
two-compartment model. More than half of patients in our trial had escalated
dose in the second cycle. So I should have inter-occasion variability. But I
got a couple of questions here.

First, what parameters should be estimated with IOV? I have seen some models
with IOV on CL, but not on others (maybe because I have seen too few
models). Now I have IOV on CL, V1 and Q and it run successfully. But when I
run with either two of them, I got minimization problem. But, am I having
too many IOVs in the model?

Second, I was wondering how to model IOV. Now I have the code as
; Define IOV, DESC = DOSE ESCALATION
  DESC=0
  IF (TIME.GE.100) DESC=1
  ETCL = ETA(1) + DESC*ETA(5)
  ETV1 = ETA(2) + DESC*ETA(6)
  ETQ = ETA(3) + DESC*ETA(7)
  ETV2 = ETA(4)

So IOV is modeled as additive relationship to IIV. But what about
multiplying relationship? Like

; Define IOV, DESC = DOSE ESCALATION
  DESC=0
  IF (TIME.GE.100) DESC=1
  ETCL = ETA(1)*(1+DESC*ETA(5))
  ETV1 = ETA(2)*(1+DESC*ETA(6))
  ETQ = ETA(3)*(1+DESC*ETA(7))
  ETV2 = ETA(4)

When I run with this multiplying relationship, I got increased OFV and
minimization terminated due to rounding error. But I didn't understand why
it is not working.

Thank you so much for your patience and time!

Jia

Received on Tue Nov 10 2009 - 21:02:36 EST

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