From: "Gerard Box" <pkpd@hotmail.com>
Subject: parent drug & metabolite
Date: Mon, 23 Apr 2001 22:59:05 -0000
Dear nmusers,
I would like to characterise the pk of parent drug and metabolite in the same run. A single oral dose of the parent compound is administered to healthy volunteers and parent drug + metabolite are sampled in blood.
In the NONMEM input file, dosing of parent compound following oral administration is in compartment 1, whereas blood concentrations of both parent drug and metabolite are in compartment 2. How does one define the input row for the metabolite, since it is not actually administered? Is it a fraction F of the dose in compartment 1 or are there other tricks to solve this problem?
Kind regards,
Gerard
parent drug & metabolite
From: bvatul <bvatul@ufl.edu>
Subject: Re: parent drug & metabolite
Date: Tue, 24 Apr 2001 09:28:53 -0400
Hello
For characterising the pk of and drug you can specify CMT=1 for dose compartment, CMT=1 for your drug and CMT=2 for your metabolite. Your error structure should have a suitable switch for CMT 1 and 2. Also you can use a hypothetical volume for your metabolite or set the scaling factor same as for your drug. In case you know the bioavailability or fraction of drug converted to metabolite you can also apply the factors accordingly.
I hope this helps
Atul
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: parent drug & metabolite
Date: Tue, 24 Apr 2001 09:45:32 -0400
Most likely, you will define your parent-metabolite model either via differential equations, ADVANs 6,8, or 9, or by using general linear models, ADVANS 5 or 7. Your model will determine the appropriate CMT to use for for doses, parent observations and metabolite observations. e.g. CMT=1 for dose records of parent drug to the oral depot, CMT=2 for parent observations in a central compartment (defined by your model), and CMT=whatever, depending on how the metabolite compartment is defined in your model (not necessarily CMT=2).
Regarding the dose of metabolite, if modeling parent and metabolite simultaneously, you may have to assume all parent is converted to metabolite (unless you have additional info, like parent concentrations in urine, etc.), otherwise you may have an identifiability problem.
Bill
From: "Bachman, William" <bachmanw@globomax.com>
Subject: RE: parent drug & metabolite
Date: Tue, 24 Apr 2001 09:58:59 -0400
It's also not necessarily CMT=3! Depends on the model. If you assume direct converion of parent to metabolite in your model, it could be 3. If there are intermediate metabolites that you may not measure, it could possibly be 4 or 5.
Bill
From: bvatul <bvatul@ufl.edu>
Subject: Re: parent drug & metabolite
Date: Tue, 24 Apr 2001 10:02:27 -0400
Hello
It was a mistake. I should have written CMT=3 for metabolite. It is not CMT=2.
Atul