Looking for ways to

For more information about TNO’s solutions to address critical factors

address the critical factors in bioavailability and PK,
please contact us. in bioavailability and PK?
Christiaan Kalk, MSc
E Christiaan.kalk@tno.nl
T +31 306 94 44 99

Steven Erpelinck, BSc

E steven.erpelinck@tno.nl
T +31 30 694 43 18

Tineke Meijers, PhD

Email: tmeijers@tnopharma.com
T +1 41 68 37 75 00
About TNO

TNO is one of Europe’s largest research and
technology organizations. We aim to provide our
customers with the best possible advice and
research based on a multidisciplinary approach and a
strong drive to give you the information you need
to optimize your drug development portfolio.
In the US, we have a strategic collaboration with the
consultancy based CRO, Seventh Wave, and Rutgers
University concerning our gastrointestinal model TIM.
Visiting address Postal address
Utrechtseweg 48 P.O. Box 360
3704 HE Zeist 3700 AJ Zeist
The Netherlands The Netherlands
www.tno.nl/pharma
TNO | Innovation for Life
 TNO services

As an expert in the critical factors in biovailability

and kinetics, TNO’s objective is to deliver the detailed
information you need for your drug development
programs. We help you address the luminal
performance and availability for absorption of
formulated API’s, biodistribution and metabolism.

We offer: TNO at the AAPS

•
Dynamic in vitro model of the gastrointestinal tract
(TIM system, see illustration below)
FIP World Congress
Addressing critical factors
in bioavailability and PK •
Unique transporter assays
(e.g. based on HEK or MDCK cells)
November 14–18, 2010, the AAPS and the FIP
World Congress will be joining forces to organize

Many of today’s drug candidates pose challenges •

In vivo and in vitro ADME studies via all routes
of application
a conference in New Orleans, USA. TNO is looking
forward to attending the conference. It is a prime
during development, for example because of their
•
In silico modeling (TIMpk, PBPK) opportunity to meet others, both new contacts and
poor permeability or drug-drug interactions.
•
Microdosing old friends, to discuss hot topics in their companies,

If you are looking for a partner to help determine •

Consultancy within TNO and in the field of drug formulation.
If you will also be attending, feel free to make an
and then address these challenges—be it a single appointment to meet with one of the TNO experts.
l transit
Gastrointestina
factor or a whole chain of different factors limiting
move
and intestine
The contents
in small portio
of the stomach
ns through the
happens here
model, just as
through the
they
Alternatively, visit our booth 2737 where we will be
Peristalsis do in reality. This
the bioavailability and metabolism of your drug
using
wall is simulated taltic valves.
explaining our approach to tackling the challenges of
The intestinal located peris
vertically
sleeves that are
flexible plastic

the
intestine
this Contents of the
water pressure;

r insight into stinal tract

compressed by in the

candidate—we at TNO would like to speak with you. lates peristalsis

Crystal-clea
therefore simu
gastrointestina
l tract.
drug development.
st ro in te
f the ga
discharge
Water supply and

dynamics o gastrointestinal tract when food

re
Nitrogen pressu ltic
closes the perista
is digested valves
ro-Intestinal
tly that goes
on in the n for TIM, the
TNO gast and small Our posters:
•
What is it exacswallowed? That’s a questiomodels, one for the stomachmodels
or medication simulation TIM-2. These The flexible
are two separate stine or colon, temperature but also the sleeve is closed
Model. There
inte stin e,
simulate not
TIM
the large inte
t:
y
-1, and one for of enzymes and bile at bod kneading and transporting
only the action the gastrointestinal trac ly be adapted for various
by nitrogen
pressure
In vitro evaluation of postprandial disintegration
hing activity of can fairly easi lt or the
most eye-catc es for a realistic model thatsystem of a baby or an adu to simulate
food. This mak
research purp a form
the digestive
oses, whether ulation. TIM-1 and TIM-2
crea
are also suitable
tures like dog
s.
Glass
of immediate release fosamprenavir tablets using
from stomach
release of a druginal tract for other single
sleeve

the dynamic gastrointestinal system TIM

Flexible plastic

the gastrointest

•
TIM-2 simulates the
d system that
ts TIM-2 is a close This system
Intestine conten allows (large intestine).

Assessment of species differences in the inhibition

small compartment
A sensor in thisthe colon model to be action of the colon particular
the volume in adjusted for a
es can be specifically porate the
Digestive juic
regulated
, and can incor
juices and target study group adult or even
saliva, gastric flora of a child
, an
Enzymes from intestinal micro
of the human and murine ABC transporters MDR1
the
are supplied for
pancreatic juice hydrates. a dog.
proteins and carbo
digestion of fats,

Stomach
(ABCB1) and Mdr1a (Abcb1a) by registered drugs
The undigested small
material of the here in

in vitro
can intestine arrives model
A pH electrode
the colon

•
By flushing the
contents with of measure the acidity
is cleared
nitrogen, the colon level
oxygen

Duodenum
Assessment whether ABC transporters are involved
pH electrode added
Bicarbonate is

Duodenum
in the duodenum
enable the pH
to
of the
in the transport of the oxime HI-6 across the blood-
ach
supplied stom
content to rise
to 6.3,
brain barrier
•
bile and
together with
pancreatic juice.

Dynamic GI tract system predicts the bioavailability

Coloncompar timent

Dialysis is system that

is also a dialys

Jejunum
Jejunum
In the jejunum
a little
In TIM-2 there
simulates the
(as formed by
absorption of
the bacteria in
water and mole
cules
the colon) by the of formulated dissolution rate API in dogs and
again
bicarbonate is of the colon.

Membrane
added; the pH
is 6.8. intestinal wall
humans. Join poster with Abbott.
system
m Flexible plastic
A dialysis syste Contents of the sleeve
intestine
simulates the
water,
absorption of Ileum
and pH Dialysis system
digested food In the ileum the
released drugs gh
Ileum rises to 7.2 throu
through the the addition of
in
intestinal wall bicarbonate.
the jejunum and
ileum.

aar@tno.nl,
Info: rob.haven
r@tno.nl
evelijn.zeijdne
for the
ts Water supply system
Compartmen specific Body tempera
ture peristalsis
ent has its own peristalsis also
Each compartm ly as possible to simulate the
resemble as close The water used temperature.
conditions that l tract. For l at the right body
l gastrointestina keeps the mode
those of the actua ach has a very
lly empty stom
instance, a virtua g and goes down
rises during eatin
low pH, which
ic acid secretion.
again by gastr