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

From: Leonid Gibiansky <lgibiansky>
Date: Fri, 6 Aug 2021 18:25:19 -0400

one can do it by hands, like set F1=1 and then use

DA1/dt = -KA*A(1)
DA2/dt = FF1(any function of time)*A(1) ..

will it do the trick?

Leonid

On 8/6/2021 4:20 PM, Robin Michelet wrote:
> 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
>> Behalf
>> 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 - 18:25:19 EDT

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