NONMEM Users Network Archive

Hosted by Cognigen

RE: time-dependent residual error models

From: Mats Karlsson <mats.karlsson>
Date: Thu, 24 Sep 2009 09:05:10 +0200

Hi Nick,

I can't answer for Phylinda, but the general idea is to build the most
appropriate structural model that is supported by data. However, after that
is done, if there still is variation in residual error magnitude one should
take that into account and not ignore it. All models are wrong, and I would
say that in general our models for absorption are more wrong than our models
for disposition. That is not just because we have focused more on the
latter, but because the underlying processes governing absorption are of a
different nature (e.g. with discrete events like food intake, gastric
emptying, bile release and formulation disintegration and movement). Further
often part of the error magnitude is from timing errors. Such errors are
more pronounced when concentrations are changing fast (normally fastest
changes in absorption phase). We wrote on time-varying residual errors (and
alternatives such as residual error magnitude related to rate of change) in
these publications:
J Pharmacokinet Biopharm. 1995 Dec;23(6):651-72.
J Pharmacokinet Biopharm. 1998 Apr;26(2):207-46

Best regards,

Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003

-----Original Message-----
From: owner-nmusers
Behalf Of Nick Holford
Sent: Thursday, September 24, 2009 7:46 AM
To: nmusers
Subject: Re: [NMusers] time-dependent residual error models


If Phylinda reads this I'd be interested to hear why she choose to use a
plain vanilla first-order absorption model and a fancy time-dependent
residual error model rather than trying to model a fancy absorption
process with a plain vanilla residual error model?


Joseph Standing wrote:
> Xiang,
> There is a rather elegant time-dependent residual error model
> described by Phylinda Chan et al in:
> BJCP, 2008;65(S1):76-85.
> BW,
> Joe

Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
mobile: +64 21 46 23 53
Received on Thu Sep 24 2009 - 03:05:10 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: