4 replies to this topic

[vijay singh]

Hello,

 

same question i have asked on support.pharsight but didn't get any response so i asked on bebac forum from there i came to know that right place to ask this question is EXTRANET , So i am posting my query again here

I was wondering

Why there is need to give the upper bound and lower bound to be given

for Tscale parameter ?when it can be calculated only from levy plot ,

 

 

also can u elobrate the correlation model which are provided in

manual because as per i understood

 

(1)Fabs = Diss(Tvivo)

 

  means :- regression between Fabs(amount absorbed at time invivo) vs

Diss(Tvivo)( amount dissolved at the corresponding invivo time)

  y=x;

  y=amount absorbed at time invivo

  x=amount dissolved at the corresponding invivo time(which can be

calulated easily from any dissolution fitted function which already

i have done in invitro tab)

 

 

 

    (2)Fabs = AbsScale * Diss(Tscale * Tvivo)

 

    means :- regression between Fabs(amount absorbed at time vivo) vs

Diss(Tvivo*Tscale)( amount dissolved at the (corresponding invivo

time*Tscale))

   here what is the need of intial value or bound to be given for

Tscale which can be measured from Tvitro vs Tvivo Levy plot.

 

 y=mx

 

 y= Fabs(amount absorbed at time invivo)

 m= Absscale parameter

 

 x=amount dissolved at the (at time invivo*Tscale)

( (X) can be calulated from any dissolution fitted model eg.hill,

wiebull which already i have done in invitro tab if i have Tscale

parameter obtained from Tvitro vs Tvivo Levy plot )

 

 

 

   Also when you are performing regression(most probably linear) between

 Fabs(amount absorbed at time invivo) vs amount dissolved at the

(at time invivo*Tscale) Absscale parameter which can be calculated

by simle linear regression equation THAN WHY BOUNDS OR INITIAL VALUE

SHOULD BE GIVEN

  y=mx

 

  y= Fabs(amount absorbed at time invivo)

  x=amount dissolved at the (at time invivo*Tscale)

  m= Absscale parameter

 

 

Please correct me if i am wrong ..will be wonderfull if you can elobrate

other two model as well as Tlag can also be calculated from Levy

plots.

 

I am really feeling very bad that i have to ask you such a long

question but i really very concerned about my study and mannual is not

providing me sufficient information.

 

 

i would HIGHLY appreciateyour response

 

 

 

 

 

 

 

Regards

Vijay Singh

Mob:8977373571

[Simon Davis]

Vijay, If you have reported an issue to support before posting here, please can you include the case number so Pharsight people can check the history, I couldn't find your case in our support system just now.

 

To be honest, I 'm not really sure what your question is, you can of course calculated ESTIMATES of these values from a plot, but by fitting them in a model yo u can get a more refined estimate. If you want to fix them in the model instead just use a user-written model instead.

 

 Simon

[vijay singh]

Dear simon,

Thanks for your reply, i don't know the case number because i just wrote an e-mail to support@pharsight.com Aug 23, 2012 at 11:36 AM f.

 

well sorry that if i asked a long and blurry question so let me try again

 

 what does these correlation model mean??

for example:-

(1)Fabs = Diss(Tvivo)

 

Fabs =fraction abosrbed of all formulation(1or 2 or more )at Tvivo

Diss(Tvivo)= fraction dissolved of all formulation(1or 2 or more ) at Tvivo

 

 is it like this as i stated above?? or something else

 

and

according to you calculating Tscale from given models will give more refined value .. , can you put some light on the terms used in the (1),(2)or(3) correlation model

for example in (2)Fabs = AbsScale * Diss(Tscale * Tvivo)

 

 what is Fabs??(is it fraction abosrbed of all formulation(1or 2 or more )at Tvivo)

 AbsScale(may be that is can be parameter)

and more importantly this term is quite confusning for me is :- Diss(Tscale * Tvivo) because if it is fraction dissolved of all formulation(1or 2 or more ) at (Tscale * Tvivo) than i have to calculate Tscale first (from levy plot ) to get Diss(Tscale * Tvivo)

 

 

 

I will Highly appreciate if you can clear it

Vijay

[Linda Hughes]

For this example, (2) Fabs = AbsScale * Diss(Tscale * Tvivo), AbsScale and Tscale are parameters in this model (as are Tshift and AbsBase in the more complicated models), so Abscale and Tscale are estimated during the model fitting.

 

Absorption may occur on a different time scale than dissolution, either faster or more slowly. Tscale is the parameter that shows how these time scales differ. It is the best estimate of that time scaling over all the formulations that were specified as "Internal" formulations on the In Vitro Formulations setup.

 

'Diss' is an internal function that linearly interpolates the predicted dissolution data, i.e., the predicted data from the dissolution model that was fit to the In Vitro data.

 

Tvivo is the independent variable in the model fitting, the In Vivo times. Fabs is the dependent variable in the model fitting; it is the fraction-absorbed data which is usually obtained from the Deconvolution output in the IVIVC Workflow, unless using the "Data already deconvolved and averaged" option.

 

Below is the description of the correlation model from the Users Guide. You may also want to consider looking into one of our IVIVC training classes.

 

"The Correlation tab and Correlation Estimates panel support the creation and

validation of an InVitro-InVivo correlation model for the dissolution data mapped

to the InVitro Data panel, and the absorption data that is either generated from

the deconvolution step in the InVivo tab or is mapped to the InVivo Fit panel.

The correlation is built using the formulations identified as Internal in the InVitro

Formulation tab. The IVIVC object fits the selected correlation model to absorption

data using the dissolution profiles from the InVitro Data panel as inputs to the

correlation function."

[vijay singh]

Thanks simon and ihughes, for your valuble inputs ,i think i got some idea now

vijay