From: "Ritu Lal" Ritu.Lal@XenoPort.com
Subject: [NMusers] FW: question for absorption modeling
Date: Fri, 4 Nov 2005 08:41:54 -0800
Dear NM users,
I am trying the following models for modeling the absorption phase of my
compound. This is data for a drug administered orally. Currently, I am using
ADVAN2 (one compt. oral absorption model with first order absorption and lag
time), but there is some model misspecification in the absorption phase.
These are the 2 other models I would like to try:
1. sequential first and zero-order abn with lag time, one compt model
2. only zero order absorption with lag time, one cpmpt model
How do I set up my data file (how do I enter RATE for the zero-order absorption?)
and control file for these 2 situations? Can I continue using the library models
or do I need to switch to user written subroutines?
Thanks,
Ritu
Ritu Lal, Ph.D.
Sr. Director, Pharmacokinetics and Drug Metabolism
Xenoport
3410 Central Expressway
Santa Clara, CA 95051
Phone (408)616-7199
Cell (408)483-3741
Fax (408)616-7212
e-mail ritu.lal@xenoport.com
question for absorption modeling
From: Justin Wilkins justin.wilkins@farmbio.uu.se
Subject: Re: [NMusers] question for absorption modeling
Date: Mon, 07 Nov 2005 10:42:58 +0100
Hi there,
I don't think there'll be any problem using the library routines for this. Specifying RATE=-2
indicates that the durations (as opposed to rates) of zero-order bolus doses will be calculated
by PK. For ADVAN2/TRANS2 you might use a data file structure similar to the following example:
#ID RATE TIME DV MDV AMT EVID
1 -2 0 0 1 600 1
1 0 1.55 3.98 0 0 0
1 0 3.13 4.32 0 0 0
1 0 4.78 3.22 0 0 0
2 -2 0 0 1 600 1
2 0 3.18 0.55 0 0 0
2 0 4.48 3.62 0 0 0
... and so on.
You would specify the D1 (duration of zero order infusion) parameter in the model
specification file, similarly to the below (while retaining KA):
TVCL = THETA(1) ; CL
CL = TVCL*EXP(ETA(1)) ; CL
TVV = THETA(2) ; V2
V = TVV*EXP(ETA(2)) ; V2
TVKA = THETA(3) ; KA
KA = TVKA*EXP(ETA(3)) ; KA
TVD1 = THETA(4) ; D1
D1 = TVD1*EXP(ETA(4)) ; D1
Another option to consider when dealing with awkward absorption and associated lag times
might be the transit compartment model - it's still in manuscript but a broad outline
was presented at PAGE 2004:
PAGE 13 (2004) Abstr 513 [www.page-meeting.org/?abstract=513]
Best regards
Justin
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