Dear All,
I'm trying to model in NONMEM the kinetics of two drug entities co-existing in
the blood. Since the assay cannot differentiate these two entities, I only have
the total concentration of these two in the blood. Does anyone has similar
experience? Can you please share the NONMEM code?
Thanks,
Yaming
Yaming Hang, Ph.D.
Pharmacometrics
Biogen Idec
14 Cambridge Center
Cambridge, MA 02142
Office: 781-464-1741
Fax: 617-679-3463
Email: [email protected]<mailto:[email protected]>
modeling of total concentration of two drugs with different kinetics in NONMEM
Dear Yaming
I have two questions.
1.Were the drugs given at the same time as a fixed dose combination?
2. Do you have PK when the drugs are give separately?
>>> Yaming Hang <[email protected]> 2012/04/25 03:22 PM >>>
Dear All,
I’m trying to model in NONMEM the kinetics of two drug entities co-existing in
the blood. Since the assay cannot differentiate these two entities, I only have
the total concentration of these two in the blood. Does anyone has similar
experience? Can you please share the NONMEM code?
Thanks,
Yaming
Yaming Hang, Ph.D.
Pharmacometrics
Biogen Idec
14 Cambridge Center
Cambridge, MA 02142
Office: 781-464-1741
Fax: 617-679-3463
Email: [email protected]
###
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Yaming,
Code should not be the problem, you just model each of them separately (say, A(1) for drug 1 and A(2) for drug 2) and then combine them as
Y=A(1)/V1 + A(2)/V2 + error.
What is more difficult to to identify parameters of each drug when you have only combined measurements. This can not be discussed in general, it is specific to each problem.
Good example is monoclonal antibodies where you have total antibody concentration measured while the blood contains free antibody + antibody bound to the target.
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 4/25/2012 9:22 AM, Yaming Hang wrote:
> Dear All,
>
> I’m trying to model in NONMEM the kinetics of two drug entities
> co-existing in the blood. Since the assay cannot differentiate these two
> entities, I only have the total concentration of these two in the blood.
> Does anyone has similar experience? Can you please share the NONMEM code?
>
> Thanks,
>
> Yaming
>
> Yaming Hang, Ph.D.
>
> Pharmacometrics
>
> Biogen Idec
>
> 14 Cambridge Center
>
> Cambridge, MA 02142
>
> Office: 781-464-1741
>
> Fax: 617-679-3463
>
> Email: [email protected] <mailto:[email protected]>
Hi Yaming,
This simplifies things significantly. The first dose will (hopefully fully)
define the PK of drug 1. The dose of drug 2 will be modeled as the sum of the
two.
Since you have only drug 1 at the beginning, you should be able to model the
full time course with:
F=A(2)/V2 + A(3)/V3
Then for the first few days, A(3)/V3 (concentration of drug 2) will be zero.
Thanks,
Bill
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Yaming Hang
Sent: Wednesday, April 25, 2012 10:43 AM
To: Retsilisitsoe Moholisa; [email protected]
Subject: RE: [NMusers] modeling of total concentration of two drugs with
different kinetics in NONMEM
Hi Retsilisitsoe,
The two drugs are given at different time (a few days apart). The first drug is
a maintenance drug without dosing history, but subjects are assumed to wash out
the drug sufficiently. In period 1, subjects were given a single IV infusion of
first drug, a few days later, subjects were given the second drug (IV infusion
again), where the first drug is not necessarily completely cleared.
Thanks,
Yaming
From: Retsilisitsoe Moholisa [mailto:[email protected]]
Sent: Wednesday, April 25, 2012 10:23 AM
To: Yaming Hang; [email protected]
Subject: Re: [NMusers] modeling of total concentration of two drugs with
different kinetics in NONMEM
Dear Yaming
I have two questions.
1.Were the drugs given at the same time as a fixed dose combination?
2. Do you have PK when the drugs are give separately?
>>> Yaming Hang <[email protected]<mailto:[email protected]>>
>>> 2012/04/25 03:22 PM >>>
Dear All,
I’m trying to model in NONMEM the kinetics of two drug entities co-existing in
the blood. Since the assay cannot differentiate these two entities, I only have
the total concentration of these two in the blood. Does anyone has similar
experience? Can you please share the NONMEM code?
Thanks,
Yaming
Yaming Hang, Ph.D.
Pharmacometrics
Biogen Idec
14 Cambridge Center
Cambridge, MA 02142
Office: 781-464-1741
Fax: 617-679-3463
Email: [email protected]<mailto:[email protected]>
###
UNIVERSITY OF CAPE TOWN
This e-mail is subject to the UCT ICT policies and e-mail disclaimer published
on our website at http://www.uct.ac.za/about/policies/emaildisclaimer/ or
obtainable from +27 21 650 9111. This e-mail is intended only for the person(s)
to whom it is addressed. If the e-mail has reached you in error, please notify
the author. If you are not the intended recipient of the e-mail you may not
use, disclose, copy, redirect or print the content. If this e-mail is not
related to the business of UCT it is sent by the sender in the sender's
individual capacity.
###