NONMEM Users Network Archive

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Re: Time-varying input/flexibility to change input rate on the fly

From: Robin Michelet <robin.michelet>
Date: Fri, 6 Aug 2021 22:20:35 +0200

Hi Bill,

Thank you for your quick answer. As far as I understand Nonmem's inner
workings, bio availability is only applied at the onset of dosing and
adding variability on it would not be able to capture a transient change
in input. For example in the case of a patch, if it would detach partly
during the dosing interval one would still need an input (i.e.
infusion-style input in the depot) but it would just be lower than
before. Changing F1 would in this case not do much right?

Kind regards,

Robin

Dr. ir. Robin Michelet
Senior scientist

Freie Universitaet Berlin
Institute of Pharmacy
Dept. of Clinical Pharmacy & Biochemistry
Kelchstr. 31
12169 Berlin
Germany
Phone: + 49 30 838 50659
Fax: + 49 30 838 4 50656
Email: robin.michelet
www.clinical-pharmacy.eu
https://fair-flagellin.eu/

On 06-08-21 10:15 PM, Bill Denney wrote:
> Hi Robin,
>
> I don't think that I've seen an update. That said, the need I had then was
> for a very specific need for an unusual drug. I've only seen this type of
> issue once where it seemed to need time-dependent effects. Generally,
> effects similar-- but not identical-- to what I was experiencing at the time
> are better-modeled with simpler systems. For example, adsorption to
> infusion sets can almost always be modeled as a decrease in bioavailability
> and/or a lag time (it's not typically time-dependent behavior).
>
> I would assume that loss of part of a tablet or detachment of a patch could
> be simply modeled as random variability (or a fixed effect) on
> bioavailability. Random pump malfunction would depend on how it
> malfunctioned, but I would be wary of trying to model random effects as this
> more complex time-dependent bioavailability unless you had data on the
> malfunction method-- in which case I would suggest putting it into the
> dataset as a different dosing record.
>
> Thanks,
>
> Bill
>
> -----Original Message-----
> From: owner-nmusers
> Of Robin Michelet
> Sent: Friday, August 6, 2021 3:38 PM
> To: nmusers
> Subject: [NMusers] Time-varying input/flexibility to change input rate on
> the fly
>
> Dear all,
>
> I was wondering if any progress has been made on the topic raised originally
> by Bill Denney in 2018:
>
> https://www.mail-archive.com/nmusers
>
> Are there any simpler ways in NM 7.5 to adapt input (e.g. infusion
> rates) in $DES during the integration step without adapting the dataset
> itself? I.e. to model the malfunctioning of an infusion pump (at random),
> the loss of part of a tablet, or the detachment of a patch?
>
> Thank you! I could not answer to the original topic which is why I just
> linked to it.
>
> --
> Dr. ir. Robin Michelet
> Senior scientist
>
> Freie Universitaet Berlin
> Institute of Pharmacy
> Dept. of Clinical Pharmacy & Biochemistry Kelchstr. 31
> 12169 Berlin
> Germany
> Phone: + 49 30 838 50659
> Fax: + 49 30 838 4 50656
> Email: robin.michelet
> www.clinical-pharmacy.eu
> https://fair-flagellin.eu/
Received on Fri Aug 06 2021 - 16:20:35 EDT

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