From: "Samtani, Mahesh [PRDUS]" MSamtani@prdus.jnj.com
Subject: [NMusers] ka and Duration
Date: Sat, 7 Jan 2006 15:45:27 -0500

Hello,
Is it possible to specify the duration of a first order input and fit ka
in NONMEM without using DEQs and IF/THEN statements? We are trying to
model the PK of a drug with simple 2-compartment disposition. The drug
is delivered by a formulation that is applied for 7 days and delivers
drug by first order input.

Kindly advise,
Mahesh

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Mahesh N. Samtani, Ph.D.
Scientist, Advanced PK-PD Modeling & Simulation
Clinical Pharmacology and Experimental Medicine
Johnson & Johnson Pharmaceutical R&D
PRD 2723, Raritan, NJ 08869
PH # (908) 704-5367
Email: msamtani@prdus.jnj.com
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 
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From: "Gastonguay, Marc" marcg@metrumrg.com
Subject: Re: [NMusers] ka and Duration
Date: Sat, 07 Jan 2006 16:49:58 -0500

Dear Mahesh,
You can limit the duration of a first order input by turning off the depot
compartment at the time the first-order process ends. This method requires the
use of PREDPP and is done through the NMTRAN data set. For example, if you have
a 100 mg transdermal patch administration for 7 days, the patch is compartment
1 and the central compartment is 2:

ID  TIME  CMT  AMT  EVID DV
1   0     1    100  1    .
; insert concentration observation records - for example
1   2     2    .    0    23 .
.
.

1   7     -1   .    2    .
1   7     1    .    2    . ; insert concentration observations and additional dosing records as needed

...where TIME is in days and AMT is in mg

The negative CMT number at TIME=7 signifies a reset to zero for that compartment
only, and is implemented on an "OTHER" data record (EVID=2). I've turned the
compartment on again at the same time by the following record with TIME=7 and
CMT=1, in case you want to add additional doses at later times. You will need to
turn off the depot compartment anytime you want to limit the duration of the
first-order input. No changes are necessary in the control stream; estimate KA
as you normally would. Be aware that when you use this method, your model could
result in less than complete absorption of the total amount of drug administered
(e.g. drug remaining in the patch after removal).

Hope this helps.
Marc

Marc R. Gastonguay, Ph.D.
marcg@metrumrg.com

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From: "Abutarif, Malaz" malaz.abutarif@spcorp.com
Subject: RE: [NMusers] ka and Duration
Date: Sat, 7 Jan 2006 18:10:17 -0500

Mahesh,
You can reset the "dosing" compartment to zero after 7 days which will effectively stop absorption.  
 
Hope that helps
Malaz
 
 

Malaz A. AbuTarif,
B.Sc. (Pharmacy), Ph.D., G.C.P.M.
Associate Principal Scientist
Schering- Plough Research Institute
2015 Galloping Hill Rd, K-15-2-2650
Kenilworth, NJ 07033
Tel: (908) 740-3835, Fax: (908) 740-2916
malaz.abutarif@spcorp.com 
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