Dear NMusers,
I am modeling long-acting injectable formulation using transit compartment
model parameterized with mtt (mean transit time) and ntr (number of transit
compartment). As I would like to model multiple formulations using the same
structure model, adding formulation as a categorical covariate on mtt or
ntr separately decreased the OFV significantly (by ~100 units). Considering
mtt and ntr are correlated parameters, should I add formulation on both
mtt and ntr, or adding to either one is sufficient?
Any input is greatly appreciated,
Jing
PS: I am considering the latter one, due to that the simulations with
changing Ktr or ntr generated similar profiles (Fig1 c and d,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636497/pdf/psp201314a.pdf).
covariate on transit compartment model parameters
Jing,
I think this is a strategy should be guided by the key questions you are
trying to address with your model. If your goal is simply to best
approximate the shape of the profile in existing individuals, the strategy
you employ could be vastly different than if the next step would be to
simulate potential impact of changes to the formulation, in which your
placement and justification of covariates could have greater implications
on your resulting inferences.
That said, I would suggest considering the mechanism of the formulation
release. For example, if these are the similar formulations, with just
tweaked adjuvant ratios to control the release rate, you could argue that
mtt alone could drive the shape changes. If, on the other hand, these
formulations had separate formulations (say different types of microsphere
formulations) that could change the mechanism of dispersal *and* the rate
of dissolution then you could tie back the contributions in shape to both
ntr and mtt.
Devin Pastoor
Center For Translational Medicine, University of Maryland Baltimore
Quoted reply history
On Sun, Sep 25, 2016 at 9:01 AM Jing Niu <[email protected]> wrote:
> Dear NMusers,
> I am modeling long-acting injectable formulation using transit compartment
> model parameterized with mtt (mean transit time) and ntr (number of transit
> compartment). As I would like to model multiple formulations using the same
> structure model, adding formulation as a categorical covariate on mtt or
> ntr separately decreased the OFV significantly (by ~100 units). Considering
> mtt and ntr are correlated parameters, should I add formulation on both
> mtt and ntr, or adding to either one is sufficient?
> Any input is greatly appreciated,
> Jing
>
> PS: I am considering the latter one, due to that the simulations with
> changing Ktr or ntr generated similar profiles (Fig1 c and d,
> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636497/pdf/psp201314a.pdf).
>
>
Hi Jing,
Testing covariates on dispostition of your long acting injectable all depends on the pharmaceutics. E.g., if you have an intramuscularly injection of a nano-suspension, you might want to consider a zero order process for the release of the drug in the systemic circulation and see whether particle size impacts dissolution rate. In any case, think about the pharmaceutical plausability first before testing a covariate.
Cheers,
Rob
Quoted reply history
Van: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] Namens Jing Niu
Verzonden: zondag 25 september 2016 14:41
Aan: nmusers_at_globomaxnm.com
Onderwerp: [NMusers] covariate on transit compartment model parameters
Dear NMusers,
I am modeling long-acting injectable formulation using transit compartment model parameterized with mtt (mean transit time) and ntr (number of transit compartment). As I would like to model multiple formulations using the same structure model, adding formulation as a categorical covariate on mtt or ntr separately decreased the OFV significantly (by ~100 units). Considering mtt and ntr are correlated parameters, should I add formulation on both mtt and ntr, or adding to either one is sufficient?
Any input is greatly appreciated,
Jing
PS: I am considering the latter one, due to that the simulations with changing Ktr or ntr generated similar profiles (Fig1 c and d, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636497/pdf/psp201314a.pdf).
Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.
Hi Jing,
Testing covariates on dispostition of your long acting injectable all depends
on the pharmaceutics. E.g., if you have an intramuscularly injection of a
nano-suspension, you might want to consider a zero order process for the
release of the drug in the systemic circulation and see whether particle size
impacts dissolution rate. In any case, think about the pharmaceutical
plausability first before testing a covariate.
Cheers,
Rob
Quoted reply history
Van: [email protected] [mailto:[email protected]] Namens
Jing Niu
Verzonden: zondag 25 september 2016 14:41
Aan: [email protected]
Onderwerp: [NMusers] covariate on transit compartment model parameters
Dear NMusers,
I am modeling long-acting injectable formulation using transit compartment
model parameterized with mtt (mean transit time) and ntr (number of transit
compartment). As I would like to model multiple formulations using the same
structure model, adding formulation as a categorical covariate on mtt or ntr
separately decreased the OFV significantly (by ~100 units). Considering mtt and
ntr are correlated parameters, should I add formulation on both mtt and ntr, or
adding to either one is sufficient?
Any input is greatly appreciated,
Jing
PS: I am considering the latter one, due to that the simulations with changing
Ktr or ntr generated similar profiles (Fig1 c and d,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636497/pdf/psp201314a.pdf).
Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het
handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of
the Chamber of Commerce under file number 41055629.