Back to the Top
[Ibrahim, have you considered fitting the iv and oral data simultaneously
with linked pk parameters ? Any other suggestions? - db]
I got data from an i.v. and i.m. experiment. The i.v. data was best fitted
by a two compartment open model. The i.m. data however, was best fitted by a
one compartment open model. How sound would it be to accept the absorption
constant in this situation?
Dr. Ibrahim Wasfi
Forensic Science Laboratory,
P O Box 253, Abu Dhabi,
FAX 009712 463470
Back to the Top
[A few replies - db]
From: "David Nix"
Date: Tue, 1 Sep 1998 16:51:27 MST7
Subject: Re: PharmPK IV and PO data with different 'number' of compartmen
Most likely, the distribution phase is obscured by the relatively
slow drug input. There are two good ways to address this issue,
however, they may or may not work in your particular case.
1. Are the data from a cross-over study? If so, consider
co-modeling the IV and IM data using a two compartment model
and sharing the parameters other than ka. This may work if
the inter-occasion variability is reasonably small. Often,
the fits will look poor if the disposition parameters change
between the dosing days.
2. If the data are not from a cross over study, then the same
simultaneous fitting can be performed using population
modeling. Here again there may be systematic differences in
the disposition parameters. Hopefully you will find some way
to help explain these differences. Inter-occasion variability
can be modeled, but I have not tried it in this circumstance.
Whether the ka values from using a one compartment model are useful
depends on the purpose of looking at ka. If truely accurate ka
values are needed then one of the techniques above should be tried.
From: "Jeff Wald"
Subject: RE: PharmPK IV and PO data with different 'number' of compartments.
Date: Tue, 1 Sep 1998 15:09:27 -0400
X-Priority: 3 (Normal)
Ibrahim - What if there were flip-flop kinetics following im administration?
Even if there is not flip-flop in the terminal phase, it is likely to be the
reason that you have lost the 'shallow' compartment in your data. The
meaning of rate-constants in these cases can be hard to interpret.
I concur with db's comment, and I would fit im and iv simultaneously.
Jeff Wald, Ph.D.
5620 Dillard Drive
Cary, NC 27511
Date: Tue, 1 Sep 1998 17:03:30 -0400 (EDT)
From: JOGARAO VS GOBBURU
cc: Multiple recipients of PharmPK - Sent by
Subject: Re: PharmPK IV and PO data with different 'number' of compartments.
It is always a good practise to fit all data pertaining to a drug
simultaneously (various doses, routes, ..). You have to fit the IV and IM
data together. The ratio of the rate constants for absorption and
distribution dictate the signature of the PK curve.
Center for Drug Development Science
Room NE 405 Med-Dent Building
3900 Reservoir Road NW,
Washington, DC 20007.
Ph : 202-687-7779
Date: Wed, 02 Sep 1998 09:52:19 -0500
From: Dr Ted Whittem
Subject: Re: PharmPK IV and PO data with different 'number' of
If you cannot simultaneously fit the IV and IM data, you could try a
Back to the Top
In my opinion, the explanation proposed by David Nix is OK and,
according to my experience, his solutions too. I suggest you to keep
them in mind because finding a lower "number" of compartments after
p.o. administration is not uncommon.
Unitat de Farmacologia i Farmacognosia
Departament de Farmacologia i Quimica Terapeutica
Facultat de Farmacia
Universitat de Barcelona
Avgda. Diagonal 643
08028 Barcelona (Spain)
Tel. (93) 4024531
Fax. (93) 4021886
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (email@example.com)