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RE: [NMusers] Simultaneous pk model of 2 drugs

From: Penland, Chris <Chris.Penland_at_astrazeneca.com>
Date: Tue, 6 Sep 2016 14:36:22 +0000

Thanks to many who have responded –

To Pavel and Rob, yes the goal is to simultaneously model the two drugs (one peptide, one small molecule) – the interaction is putatively through a dynamic effect of one drug on renal function that one is partially dependent on and the other is highly dependent on. Both are active against the same PD marker.

Regards to all
-chris


From: R.terHeine_at_radboudumc.nl [mailto:R.terHeine_at_radboudumc.nl]
Sent: Tuesday, September 06, 2016 7:35 AM
To: nonmem_at_optonline.net; Penland, Chris
Cc: nmusers_at_globomaxnm.com
Subject: RE: [NMusers] Simultaneous pk model of 2 drugs

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> [mailto:owner-nmusers_at_globomaxnm.com] Namens Pavel Belo
Verzonden: dinsdag 6 september 2016 3:04
Aan: Penland, Chris
CC: nmusers_at_globomaxnm.com<mailto: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 - 10:36:22 EDT

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