NONMEM Users Network Archive

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Re: PK data from individuals who vomited after drug ingestion

From: Nick Holford <n.holford>
Date: Thu, 27 Aug 2009 17:14:44 +1200

Kok-Seng,

I would not use a mixture model because you already have the information
about which group vomited.

I am surprised you describe the elimination of ethanol with a half-life.
If you gave an ethanol dose big enough to induce vomiting I would expect
you to describe elimination with a mixed order (saturable) elimination
process.

Best wishes,

Nick

Seng Kok Yong wrote:
>
> Dear NM-users,
>
> I have a question regarding NONMEM modeling of PK data from
> individuals who vomited after drug ingestion. Basically, I have a set
> of data from about 150 subjects (about 5 measurements per subject) who
> orally ingested alcohol at time = 0 h. However, about 15% of this
> group vomited more than 1 h post-dose. Based on NONMEM modeling of PK
> data from subjects who did not vomit during the study, the mean
> elimination half-life is about 30 min.
>
> May I ask if I should model vomiting incidence (a “yes” or a “no”) as
> a categorical covariate for analysis of all the data? I have
> demographic covariate information at hand. Or, should I introduce a
> mixture model during NONMEM modeling? I would expect the vomiting
> subgroup to display different values for Vd, Ka etc as compared to the
> non-vomiting subgroup.
>
> Thank you very much for your time and kind advice.
>
> Best wishes,
>
> Kok-Yong Seng, PhD
>
> DSO National Laboratories
>
> Republic of Singapore
>

--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
n.holford
mobile: +64 21 46 23 53
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Received on Thu Aug 27 2009 - 01:14:44 EDT

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