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Re: [NMusers] Simultaneous pk model of 2 drugs

From: Masaki Hiraoka <GCA02464_at_nifty.ne.jp>
Date: Wed, 7 Sep 2016 12:40:58 +0900

Hi all,

I don't think we should do analyze two drugs simultaneously. I DO agree
that two drugs may correlate to each other through physiology.

However I think we should analyze factors in physiology first. Then we
can analyze the correlation between two drug.

Regards,

Masaki


On 2016/09/06 20:34, R.terHeine_at_radboudumc.nl wrote:
>
> Hi all,
>
> I guess that if both drugs are given to the same person, it makes a
> lot of sense to perform simultaneous modeling, because of physiology,
> a lot of parameters will show covariance. The PK of one drug can
> therefore partially explain the PK of the other one (and vice versa).
>
> Cheers,
>
> Rob
>
> **
>
> *---*
>
> *Dr. R. ter Heine, hospital pharmacist-clinical pharmacologist*
>
> *Head of Clinical Trials Unit, Dept. of Pharmacy*
>
> *Radboudumc *
>
> T +31-24-36 16405
>
> F +31-24-36 68755
>
> *Van:*owner-nmusers_at_globomaxnm.com
> [mailto:owner-nmusers_at_globomaxnm.com] *Namens *Pavel Belo
> *Verzonden:* dinsdag 6 september 2016 3:04
> *Aan:* Penland, Chris
> *CC:* nmusers_at_globomaxnm.com
> *Onderwerp:* RE: [NMusers] Simultaneous pk model of 2 drugs
>
> Hello Chris,
>
> What is the point of modeling 2 drugs in one NONMEM code? Do the
> drugs interact? For example, you can have 2 monoclonal antibodies
> competing for or binding to the same target and/or concentration of
> one drug changes elimination rate or some other parameters of the
> other one. If they do not interact, you can model them separately.
> In some cases, even if they interact you can model them separately
> using dose of one drug as a covariate for the other one.
>
> Regards,
>
> Pavel
>
> On Fri, Sep 02, 2016 at 01:22 PM, Penland, Chris wrote:
>
> Greetings NMusers,
>
> Does nonmem have the capacity, unbeknownst to me, for modeling two
> simultaneous drugs?
>
> I would like some suggestions about how to define the dataset and
> model for a subcutaneous drug and oral drug being administered on
> different schedules. I would use DVID = 1 and 2 for the two plasma
> pk observations. I figure this soft of thing had to be dealt with
> in the past when trying to model dynamic DDIs (vs, just taking one
> of the drugs as a covariate on the other’s parameters).
>
> One approach is to specify the compartments for each to be dosed
> into then have those feed the central, but I’m curious to see if
> there is something more subtle in the nonmem syntax. Is there
> something about EVID, that I don’t know that would help (beyond
> EVID=1 for dosing)
>
> What if you had two oral drugs? Would you treat the two dosing
> compartments as separate and possibly link them together at the
> parameter/covariance level?
>
> Thanks,
>
> Chris
>
> Chris Penland, PhD
>
> ECD / Quantitative Clinical Pharmacology
>
> Waltham, MA USA
>
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Received on Tue Sep 06 2016 - 23:40:58 EDT

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