NONMEM Users Network Archive

Hosted by Cognigen

FW: Duration of Absorption Time From Depot as Covariate

From: Jurgen Bulitta <jbulitta>
Date: Sun, 20 Dec 2009 20:19:21 -0500

Dear Paul, Masoud, Leonid and Jeroen,

I think your comments and solutions were all excellent.
Wanted to add two comments from my experience with
around 10 IVIVC studies on sustained-release formulations.
At least for these drugs, it was 10 of 10 times possible to establish
a link between the release profile in vitro and the absorption
profiles in humans. As Leonid wrote, it is often not possible to assume
that time-in-vitro and time in vivo correlate 1:1. After applying a
nonlinear time transformation, this conversion of in-vitro-time to
in-vivo-time held up for various formulations of the same drug.
Therefore, I would not use the fraction released in vitro directly
as input-function of the amount of drug absorbed in vivo.

We developed a fairly flexible and simple absorption model [1] which can
accommodate a large range of absorption profiles including sharp peaks, "fl=
peaks", and dual peaks for cefuroxime axetil (see Fig. 2). If one does not =
have the
full data or time available to implement the elegant approaches from Kiyohi=
Martin, and Masoud, this model may be an alternative. The basic idea of the
cefuroxime model is that gastric release can be described by a Michaelis-Me=
process and that the associated Vmax can change over time (for example usin=
time past dose or time past last meal as the reference point). We have succ=
adapted this model to multiple dose data over various dose levels with or w=
between occasion variability and the model was robust in NONMEM, SADAPT, & =

Best wishes

Jurgen Bulitta, Ph.D., Senior Scientist
Ordway Research Institute, Albany, NY

[1] New semiphysiological absorption model to assess the pharmacodynamic pr=
ofile of
cefuroxime axetil using nonparametric and parametric population pharmacokin=
Bulitta JB, Landersdorfer CB, Kinzig M, Holzgrabe U, Sorgel F.
Antimicrob Agents Chemother. 2009 Aug;53(8):3462-71

Received on Sun Dec 20 2009 - 20:19:21 EST

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: